TY - GEN A1 - Gorski, Mathias A1 - Jung, Bettina A1 - Li, Yong A1 - Matias-Garcia, Pamela R. A1 - Wuttke, Matthias A1 - Coassin, Stefan A1 - Thio, Chris H. L. A1 - Kleber, Marcus E. A1 - Winkler, Thomas W. A1 - Wanner, Veronika A1 - Chai, Jin-Fang A1 - Chu, Audrey Y. A1 - Cocca, Massimiliano A1 - Feitosa, Mary F. A1 - Ghasemi, Sahar A1 - Hoppmann, Anselm A1 - Horn, Katrin A1 - Li, Man A1 - Nutile, Teresa A1 - Scholz, Markus A1 - Sieber, Karsten B. A1 - Teumer, Alexander A1 - Tin, Adrienne A1 - Wang, Judy A1 - Tayo, Bamidele O. A1 - Ahluwalia, Tarunveer S. A1 - Almgren, Peter A1 - Bakker, Stephan J. L. A1 - Banas, Bernhard A1 - Bansal, Nisha A1 - Biggs, Mary L. A1 - Boerwinkle, Eric A1 - Böttinger, Erwin A1 - Brenner, Hermann A1 - Carroll, Robert J. A1 - Chalmers, John A1 - Chee, Miao-Li A1 - Chee, Miao-Ling A1 - Cheng, Ching-Yu A1 - Coresh, Josef A1 - de Borst, Martin H. A1 - Degenhardt, Frauke A1 - Eckardt, Kai-Uwe A1 - Endlich, Karlhans A1 - Franke, Andre A1 - Freitag-Wolf, Sandra A1 - Gampawar, Piyush A1 - Gansevoort, Ron T. A1 - Ghanbari, Mohsen A1 - Gieger, Christian A1 - Hamet, Pavel A1 - Ho, Kevin A1 - Hofer, Edith A1 - Holleczek, Bernd A1 - Foo, Valencia Hui Xian A1 - Hutri-Kahonen, Nina A1 - Hwang, Shih-Jen A1 - Ikram, M. Arfan A1 - Josyula, Navya Shilpa A1 - Kahonen, Mika A1 - Khor, Chiea-Chuen A1 - Koenig, Wolfgang A1 - Kramer, Holly A1 - Kraemer, Bernhard K. A1 - Kuehnel, Brigitte A1 - Lange, Leslie A. A1 - Lehtimaki, Terho A1 - Lieb, Wolfgang A1 - Loos, Ruth J. F. A1 - Lukas, Mary Ann A1 - Lyytikainen, Leo-Pekka A1 - Meisinger, Christa A1 - Meitinger, Thomas A1 - Melander, Olle A1 - Milaneschi, Yuri A1 - Mishra, Pashupati P. A1 - Mononen, Nina A1 - Mychaleckyj, Josyf C. A1 - Nadkarni, Girish N. A1 - Nauck, Matthias A1 - Nikus, Kjell A1 - Ning, Boting A1 - Nolte, Ilja M. A1 - O'Donoghue, Michelle L. A1 - Orho-Melander, Marju A1 - Pendergrass, Sarah A. A1 - Penninx, Brenda W. J. H. A1 - Preuss, Michael H. A1 - Psaty, Bruce M. A1 - Raffield, Laura M. A1 - Raitakari, Olli T. A1 - Rettig, Rainer A1 - Rheinberger, Myriam A1 - Rice, Kenneth M. A1 - Rosenkranz, Alexander R. A1 - Rossing, Peter A1 - Rotter, Jerome A1 - Sabanayagam, Charumathi A1 - Schmidt, Helena A1 - Schmidt, Reinhold A1 - Schoettker, Ben A1 - Schulz, Christina-Alexandra A1 - Sedaghat, Sanaz A1 - Shaffer, Christian M. A1 - Strauch, Konstantin A1 - Szymczak, Silke A1 - Taylor, Kent D. A1 - Tremblay, Johanne A1 - Chaker, Layal A1 - van der Harst, Pim A1 - van der Most, Peter J. A1 - Verweij, Niek A1 - Voelker, Uwe A1 - Waldenberger, Melanie A1 - Wallentin, Lars A1 - Waterworth, Dawn M. A1 - White, Harvey D. A1 - Wilson, James G. A1 - Wong, Tien-Yin A1 - Woodward, Mark A1 - Yang, Qiong A1 - Yasuda, Masayuki A1 - Yerges-Armstrong, Laura M. A1 - Zhang, Yan A1 - Snieder, Harold A1 - Wanner, Christoph A1 - Boger, Carsten A. A1 - Kottgen, Anna A1 - Kronenberg, Florian A1 - Pattaro, Cristian A1 - Heid, Iris M. T1 - Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline T2 - Zweitveröffentlichungen der Universität Potsdam : Reihe der Digital Engineering Fakultät N2 - Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m(2)/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m(2) at follow-up among those with eGFRcrea 60 mL/min/1.73m(2) or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or (LARP4B). Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function. T3 - Zweitveröffentlichungen der Universität Potsdam : Reihe der Digital Engineering Fakultät - 19 KW - acute kidney injury KW - end-stage kidney disease KW - genome-wide association KW - study KW - rapid eGFRcrea decline Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-565379 IS - 19 ER - TY - JOUR A1 - Wuttke, Matthias A1 - Li, Yong A1 - Li, Man A1 - Sieber, Karsten B. A1 - Feitosa, Mary F. A1 - Gorski, Mathias A1 - Tin, Adrienne A1 - Wang, Lihua A1 - Chu, Audrey Y. A1 - Hoppmann, Anselm A1 - Kirsten, Holger A1 - Giri, Ayush A1 - Chai, Jin-Fang A1 - Sveinbjornsson, Gardar A1 - Tayo, Bamidele O. A1 - Nutile, Teresa A1 - Fuchsberger, Christian A1 - Marten, Jonathan A1 - Cocca, Massimiliano A1 - Ghasemi, Sahar A1 - Xu, Yizhe A1 - Horn, Katrin A1 - Noce, Damia A1 - Van der Most, Peter J. A1 - Sedaghat, Sanaz A1 - Yu, Zhi A1 - Akiyama, Masato A1 - Afaq, Saima A1 - Ahluwalia, Tarunveer Singh A1 - Almgren, Peter A1 - Amin, Najaf A1 - Arnlov, Johan A1 - Bakker, Stephan J. L. A1 - Bansal, Nisha A1 - Baptista, Daniela A1 - Bergmann, Sven A1 - Biggs, Mary L. A1 - Biino, Ginevra A1 - Boehnke, Michael A1 - Boerwinkle, Eric A1 - Boissel, Mathilde A1 - Böttinger, Erwin A1 - Boutin, Thibaud S. A1 - Brenner, Hermann A1 - Brumat, Marco A1 - Burkhardt, Ralph A1 - Butterworth, Adam S. A1 - Campana, Eric A1 - Campbell, Archie A1 - Campbell, Harry A1 - Canouil, Mickael A1 - Carroll, Robert J. A1 - Catamo, Eulalia A1 - Chambers, John C. A1 - Chee, Miao-Ling A1 - Chee, Miao-Li A1 - Chen, Xu A1 - Cheng, Ching-Yu A1 - Cheng, Yurong A1 - Christensen, Kaare A1 - Cifkova, Renata A1 - Ciullo, Marina A1 - Concas, Maria Pina A1 - Cook, James P. A1 - Coresh, Josef A1 - Corre, Tanguy A1 - Sala, Cinzia Felicita A1 - Cusi, Daniele A1 - Danesh, John A1 - Daw, E. Warwick A1 - De Borst, Martin H. A1 - De Grandi, Alessandro A1 - De Mutsert, Renee A1 - De Vries, Aiko P. J. A1 - Degenhardt, Frauke A1 - Delgado, Graciela A1 - Demirkan, Ayse A1 - Di Angelantonio, Emanuele A1 - Dittrich, Katalin A1 - Divers, Jasmin A1 - Dorajoo, Rajkumar A1 - Eckardt, Kai-Uwe A1 - Ehret, Georg A1 - Elliott, Paul A1 - Endlich, Karlhans A1 - Evans, Michele K. A1 - Felix, Janine F. A1 - Foo, Valencia Hui Xian A1 - Franco, Oscar H. A1 - Franke, Andre A1 - Freedman, Barry I. A1 - Freitag-Wolf, Sandra A1 - Friedlander, Yechiel A1 - Froguel, Philippe A1 - Gansevoort, Ron T. A1 - Gao, He A1 - Gasparini, Paolo A1 - Gaziano, J. Michael A1 - Giedraitis, Vilmantas A1 - Gieger, Christian A1 - Girotto, Giorgia A1 - Giulianini, Franco A1 - Gogele, Martin A1 - Gordon, Scott D. A1 - Gudbjartsson, Daniel F. A1 - Gudnason, Vilmundur A1 - Haller, Toomas A1 - Hamet, Pavel A1 - Harris, Tamara B. A1 - Hartman, Catharina A. A1 - Hayward, Caroline A1 - Hellwege, Jacklyn N. A1 - Heng, Chew-Kiat A1 - Hicks, Andrew A. A1 - Hofer, Edith A1 - Huang, Wei A1 - Hutri-Kahonen, Nina A1 - Hwang, Shih-Jen A1 - Ikram, M. Arfan A1 - Indridason, Olafur S. A1 - Ingelsson, Erik A1 - Ising, Marcus A1 - Jaddoe, Vincent W. V. A1 - Jakobsdottir, Johanna A1 - Jonas, Jost B. A1 - Joshi, Peter K. A1 - Josyula, Navya Shilpa A1 - Jung, Bettina A1 - Kahonen, Mika A1 - Kamatani, Yoichiro A1 - Kammerer, Candace M. A1 - Kanai, Masahiro A1 - Kastarinen, Mika A1 - Kerr, Shona M. A1 - Khor, Chiea-Chuen A1 - Kiess, Wieland A1 - Kleber, Marcus E. A1 - Koenig, Wolfgang A1 - Kooner, Jaspal S. A1 - Korner, Antje A1 - Kovacs, Peter A1 - Kraja, Aldi T. A1 - Krajcoviechova, Alena A1 - Kramer, Holly A1 - Kramer, Bernhard K. A1 - Kronenberg, Florian A1 - Kubo, Michiaki A1 - Kuhnel, Brigitte A1 - Kuokkanen, Mikko A1 - Kuusisto, Johanna A1 - La Bianca, Martina A1 - Laakso, Markku A1 - Lange, Leslie A. A1 - Langefeld, Carl D. A1 - Lee, Jeannette Jen-Mai A1 - Lehne, Benjamin A1 - Lehtimaki, Terho A1 - Lieb, Wolfgang A1 - Lim, Su-Chi A1 - Lind, Lars A1 - Lindgren, Cecilia M. A1 - Liu, Jun A1 - Liu, Jianjun A1 - Loeffler, Markus A1 - Loos, Ruth J. F. A1 - Lucae, Susanne A1 - Lukas, Mary Ann A1 - Lyytikainen, Leo-Pekka A1 - Magi, Reedik A1 - Magnusson, Patrik K. E. A1 - Mahajan, Anubha A1 - Martin, Nicholas G. A1 - Martins, Jade A1 - Marz, Winfried A1 - Mascalzoni, Deborah A1 - Matsuda, Koichi A1 - Meisinger, Christa A1 - Meitinger, Thomas A1 - Melander, Olle A1 - Metspalu, Andres A1 - Mikaelsdottir, Evgenia K. A1 - Milaneschi, Yuri A1 - Miliku, Kozeta A1 - Mishra, Pashupati P. A1 - Program, V. A. Million Veteran A1 - Mohlke, Karen L. A1 - Mononen, Nina A1 - Montgomery, Grant W. A1 - Mook-Kanamori, Dennis O. A1 - Mychaleckyj, Josyf C. A1 - Nadkarni, Girish N. A1 - Nalls, Mike A. A1 - Nauck, Matthias A1 - Nikus, Kjell A1 - Ning, Boting A1 - Nolte, Ilja M. A1 - Noordam, Raymond A1 - Olafsson, Isleifur A1 - Oldehinkel, Albertine J. A1 - Orho-Melander, Marju A1 - Ouwehand, Willem H. A1 - Padmanabhan, Sandosh A1 - Palmer, Nicholette D. A1 - Palsson, Runolfur A1 - Penninx, Brenda W. J. H. A1 - Perls, Thomas A1 - Perola, Markus A1 - Pirastu, Mario A1 - Pirastu, Nicola A1 - Pistis, Giorgio A1 - Podgornaia, Anna I. A1 - Polasek, Ozren A1 - Ponte, Belen A1 - Porteous, David J. A1 - Poulain, Tanja A1 - Pramstaller, Peter P. A1 - Preuss, Michael H. A1 - Prins, Bram P. A1 - Province, Michael A. A1 - Rabelink, Ton J. A1 - Raffield, Laura M. A1 - Raitakari, Olli T. A1 - Reilly, Dermot F. A1 - Rettig, Rainer A1 - Rheinberger, Myriam A1 - Rice, Kenneth M. A1 - Ridker, Paul M. A1 - Rivadeneira, Fernando A1 - Rizzi, Federica A1 - Roberts, David J. A1 - Robino, Antonietta A1 - Rossing, Peter A1 - Rudan, Igor A1 - Rueedi, Rico A1 - Ruggiero, Daniela A1 - Ryan, Kathleen A. A1 - Saba, Yasaman A1 - Sabanayagam, Charumathi A1 - Salomaa, Veikko A1 - Salvi, Erika A1 - Saum, Kai-Uwe A1 - Schmidt, Helena A1 - Schmidt, Reinhold A1 - Ben Schottker, A1 - Schulz, Christina-Alexandra A1 - Schupf, Nicole A1 - Shaffer, Christian M. A1 - Shi, Yuan A1 - Smith, Albert V. A1 - Smith, Blair H. A1 - Soranzo, Nicole A1 - Spracklen, Cassandra N. A1 - Strauch, Konstantin A1 - Stringham, Heather M. A1 - Stumvoll, Michael A1 - Svensson, Per O. A1 - Szymczak, Silke A1 - Tai, E-Shyong A1 - Tajuddin, Salman M. A1 - Tan, Nicholas Y. Q. A1 - Taylor, Kent D. A1 - Teren, Andrej A1 - Tham, Yih-Chung A1 - Thiery, Joachim A1 - Thio, Chris H. L. A1 - Thomsen, Hauke A1 - Thorleifsson, Gudmar A1 - Toniolo, Daniela A1 - Tonjes, Anke A1 - Tremblay, Johanne A1 - Tzoulaki, Ioanna A1 - Uitterlinden, Andre G. A1 - Vaccargiu, Simona A1 - Van Dam, Rob M. A1 - Van der Harst, Pim A1 - Van Duijn, Cornelia M. A1 - Edward, Digna R. Velez A1 - Verweij, Niek A1 - Vogelezang, Suzanne A1 - Volker, Uwe A1 - Vollenweider, Peter A1 - Waeber, Gerard A1 - Waldenberger, Melanie A1 - Wallentin, Lars A1 - Wang, Ya Xing A1 - Wang, Chaolong A1 - Waterworth, Dawn M. A1 - Bin Wei, Wen A1 - White, Harvey A1 - Whitfield, John B. A1 - Wild, Sarah H. A1 - Wilson, James F. A1 - Wojczynski, Mary K. A1 - Wong, Charlene A1 - Wong, Tien-Yin A1 - Xu, Liang A1 - Yang, Qiong A1 - Yasuda, Masayuki A1 - Yerges-Armstrong, Laura M. A1 - Zhang, Weihua A1 - Zonderman, Alan B. A1 - Rotter, Jerome I. A1 - Bochud, Murielle A1 - Psaty, Bruce M. A1 - Vitart, Veronique A1 - Wilson, James G. A1 - Dehghan, Abbas A1 - Parsa, Afshin A1 - Chasman, Daniel I. A1 - Ho, Kevin A1 - Morris, Andrew P. A1 - Devuyst, Olivier A1 - Akilesh, Shreeram A1 - Pendergrass, Sarah A. A1 - Sim, Xueling A1 - Boger, Carsten A. A1 - Okada, Yukinori A1 - Edwards, Todd L. A1 - Snieder, Harold A1 - Stefansson, Kari A1 - Hung, Adriana M. A1 - Heid, Iris M. A1 - Scholz, Markus A1 - Teumer, Alexander A1 - Kottgen, Anna A1 - Pattaro, Cristian T1 - A catalog of genetic loci associated with kidney function from analyses of a million individuals JF - Nature genetics N2 - Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research. Y1 - 2019 U6 - https://doi.org/10.1038/s41588-019-0407-x SN - 1061-4036 SN - 1546-1718 VL - 51 IS - 6 SP - 957 EP - + PB - Nature Publ. Group CY - New York ER - TY - JOUR A1 - Gorski, Mathias A1 - Jung, Bettina A1 - Li, Yong A1 - Matias-Garcia, Pamela R. A1 - Wuttke, Matthias A1 - Coassin, Stefan A1 - Thio, Chris H. L. A1 - Kleber, Marcus E. A1 - Winkler, Thomas W. A1 - Wanner, Veronika A1 - Chai, Jin-Fang A1 - Chu, Audrey Y. A1 - Cocca, Massimiliano A1 - Feitosa, Mary F. A1 - Ghasemi, Sahar A1 - Hoppmann, Anselm A1 - Horn, Katrin A1 - Li, Man A1 - Nutile, Teresa A1 - Scholz, Markus A1 - Sieber, Karsten B. A1 - Teumer, Alexander A1 - Tin, Adrienne A1 - Wang, Judy A1 - Tayo, Bamidele O. A1 - Ahluwalia, Tarunveer S. A1 - Almgren, Peter A1 - Bakker, Stephan J. L. A1 - Banas, Bernhard A1 - Bansal, Nisha A1 - Biggs, Mary L. A1 - Boerwinkle, Eric A1 - Böttinger, Erwin A1 - Brenner, Hermann A1 - Carroll, Robert J. A1 - Chalmers, John A1 - Chee, Miao-Li A1 - Chee, Miao-Ling A1 - Cheng, Ching-Yu A1 - Coresh, Josef A1 - de Borst, Martin H. A1 - Degenhardt, Frauke A1 - Eckardt, Kai-Uwe A1 - Endlich, Karlhans A1 - Franke, Andre A1 - Freitag-Wolf, Sandra A1 - Gampawar, Piyush A1 - Gansevoort, Ron T. A1 - Ghanbari, Mohsen A1 - Gieger, Christian A1 - Hamet, Pavel A1 - Ho, Kevin A1 - Hofer, Edith A1 - Holleczek, Bernd A1 - Foo, Valencia Hui Xian A1 - Hutri-Kahonen, Nina A1 - Hwang, Shih-Jen A1 - Ikram, M. Arfan A1 - Josyula, Navya Shilpa A1 - Kahonen, Mika A1 - Khor, Chiea-Chuen A1 - Koenig, Wolfgang A1 - Kramer, Holly A1 - Kraemer, Bernhard K. A1 - Kuehnel, Brigitte A1 - Lange, Leslie A. A1 - Lehtimaki, Terho A1 - Lieb, Wolfgang A1 - Loos, Ruth J. F. A1 - Lukas, Mary Ann A1 - Lyytikainen, Leo-Pekka A1 - Meisinger, Christa A1 - Meitinger, Thomas A1 - Melander, Olle A1 - Milaneschi, Yuri A1 - Mishra, Pashupati P. A1 - Mononen, Nina A1 - Mychaleckyj, Josyf C. A1 - Nadkarni, Girish N. A1 - Nauck, Matthias A1 - Nikus, Kjell A1 - Ning, Boting A1 - Nolte, Ilja M. A1 - O'Donoghue, Michelle L. A1 - Orho-Melander, Marju A1 - Pendergrass, Sarah A. A1 - Penninx, Brenda W. J. H. A1 - Preuss, Michael H. A1 - Psaty, Bruce M. A1 - Raffield, Laura M. A1 - Raitakari, Olli T. A1 - Rettig, Rainer A1 - Rheinberger, Myriam A1 - Rice, Kenneth M. A1 - Rosenkranz, Alexander R. A1 - Rossing, Peter A1 - Rotter, Jerome A1 - Sabanayagam, Charumathi A1 - Schmidt, Helena A1 - Schmidt, Reinhold A1 - Schoettker, Ben A1 - Schulz, Christina-Alexandra A1 - Sedaghat, Sanaz A1 - Shaffer, Christian M. A1 - Strauch, Konstantin A1 - Szymczak, Silke A1 - Taylor, Kent D. A1 - Tremblay, Johanne A1 - Chaker, Layal A1 - van der Harst, Pim A1 - van der Most, Peter J. A1 - Verweij, Niek A1 - Voelker, Uwe A1 - Waldenberger, Melanie A1 - Wallentin, Lars A1 - Waterworth, Dawn M. A1 - White, Harvey D. A1 - Wilson, James G. A1 - Wong, Tien-Yin A1 - Woodward, Mark A1 - Yang, Qiong A1 - Yasuda, Masayuki A1 - Yerges-Armstrong, Laura M. A1 - Zhang, Yan A1 - Snieder, Harold A1 - Wanner, Christoph A1 - Boger, Carsten A. A1 - Kottgen, Anna A1 - Kronenberg, Florian A1 - Pattaro, Cristian A1 - Heid, Iris M. T1 - Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline JF - Kidney international : official journal of the International Society of Nephrology N2 - Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m(2)/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m(2) at follow-up among those with eGFRcrea 60 mL/min/1.73m(2) or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or (LARP4B). Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function. KW - acute kidney injury KW - end-stage kidney disease KW - genome-wide association KW - study KW - rapid eGFRcrea decline Y1 - 2020 U6 - https://doi.org/10.1016/j.kint.2020.09.030 SN - 0085-2538 SN - 1523-1755 VL - 99 IS - 4 SP - 926 EP - 939 PB - Elsevier CY - New York ER - TY - JOUR A1 - Li, Jian A1 - Lu, Yong-Ping A1 - Tsuprykov, Oleg A1 - Hasan, Ahmed Abdallah Abdalrahman Mohamed A1 - Reichetzeder, Christoph A1 - Tian, Mei A1 - Zhang, Xiao Li A1 - Zhang, Qin A1 - Sun, Guo-Ying A1 - Guo, Jingli A1 - Gaballa, Mohamed Mahmoud Salem Ahmed A1 - Peng, Xiao-Ning A1 - Lin, Ge A1 - Hocher, Berthold T1 - Folate treatment of pregnant rat dams abolishes metabolic effects in female offspring induced by a paternal pre-conception unhealthy diet JF - Diabetologia : journal of the European Association for the Study of Diabetes (EASD) N2 - Aims/hypothesis Paternal high-fat diet prior to mating programmes impaired glucose tolerance in female offspring. We examined whether the metabolic consequences in offspring could be abolished by folate treatment of either the male rats before mating or the corresponding female rats during pregnancy. Methods Male F0 rats were fed either control diet or high-fat, high-sucrose and high-salt diet (HFSSD), with or without folate, before mating. Male rats were mated with control-diet-fed dams. After mating, the F0 dams were fed control diet with or without folate during pregnancy. KW - Glucose tolerance KW - High-fat-sucrose-salt diet KW - Maternal folate treatment KW - Paternal programming Y1 - 2018 U6 - https://doi.org/10.1007/s00125-018-4635-x SN - 0012-186X SN - 1432-0428 VL - 61 IS - 8 SP - 1862 EP - 1876 PB - Springer CY - New York ER - TY - JOUR A1 - Li, Hua A1 - Xu, Yong A1 - Li, Yongge A1 - Metzler, Ralf T1 - Transition path dynamics across rough inverted parabolic potential barrier JF - The European physical journal : Plus N2 - Transition path dynamics have been widely studied in chemical, physical, and technological systems. Mostly, the transition path dynamics is obtained for smooth barrier potentials, for instance, generic inverse-parabolic shapes. We here present analytical results for the mean transition path time, the distribution of transition path times, the mean transition path velocity, and the mean transition path shape in a rough inverted parabolic potential function under the driving of Gaussian white noise. These are validated against extensive simulations using the forward flux sampling scheme in parallel computations. We observe how precisely the potential roughness, the barrier height, and the noise intensity contribute to the particle transition in the rough inverted barrier potential. Y1 - 2020 U6 - https://doi.org/10.1140/epjp/s13360-020-00752-7 SN - 2190-5444 VL - 135 IS - 9 PB - Springer CY - Berlin ; Heidelberg ER - TY - JOUR A1 - Funk, Roger A1 - Li, Yong A1 - Hoffmann, Carsten A1 - Reiche, Matthias A1 - Zhang, Zhuodong A1 - Li, Junjie A1 - Sommer, Michael T1 - Using Cs-137 to estimate wind erosion and dust deposition on grassland in Inner Mongolia-selection of a reference site and description of the temporal variability JF - Plant and soil N2 - The aims of this study were to identify areas of wind erosion and dust deposition and to quantify the effects of different grazing intensities on soil redistribution rates in grasslands based on the Cs-137 technique. Because the method uses a reference inventory as threshold for erosion or deposition, the classification of any other site as source or sink for dust depends on the accurate selection of this reference site. Measurements of Cs-137 inventories and depth distributions were carried out at pasture sites with predominant species of Stipa grandis and Leymus chinensis which are grazed with different intensities. Additional measurements were made at arable land, plant-covered sand dunes and alluvial plains. Wind-induced soil erosion and dust deposition rates were calculated from Cs-137 inventories by means of the "Profile-Distribution" and the "Mass Balance II" models. The selection of the reference site was based on fluid dynamical and process-determining parameters. The chosen site should meet the following four conditions: (i) located at a summit position with obviously low deposition rates, (ii) sufficient vegetation cover to prevent wind erosion, (iii) plane to exclude water erosion and (iv) in the wind/dust shadow of a higher elevation. The measured reference inventory of Cs-137 was 1967(+/- 102) Bqm(-2) located at a summit position of moderately grazed Leymus chinensis steppe. The Cs-137 inventories at other sites ranged from 1330 Bqm(-2) at heavily grazed sites to 5119 Bqm(-2) at river deposits, representing annual average soil losses of up to 130 tkm(-2) and deposits of up to 540 tkm(-2), respectively. The calculated annual averages of dust depositions at ungrazed Leymus chinensis sites were related to the dust storm frequencies of the last 50 years resulting in a description of the temporal variability of annual dust depositions from about 154 tkm(-2) in the 1960s to 26 tkm(-2) at recent times. Based on this quantification already 80% of the total dust depositions can be related to the 20 years between the 1960s and the end of the 1970s and only 20% to the time between 1980 and 2001. Cs-137 technique is a promising method to assess the effect of grazing intensity and land use types on the spatial variability of wind-induced soil and dust redistribution processes in semi-arid grasslands. However, considerable efforts are needed to identify a reliable reference site, because erosion and deposition induced by wind may occur at the same places. The combination of the dust deposition rates derived from Cs-137 profile data with the dust storm frequencies is helpful for a better reconstruction of the temporal variability of dust deposition and wind erosion in this region. The calculated recent deposition rates of about 20 tkm(-2) are in good agreement with data of other authors. KW - Cs-137 KW - Grassland KW - Wind erosion KW - Dust deposition KW - Reference site Y1 - 2012 U6 - https://doi.org/10.1007/s11104-011-0964-y SN - 0032-079X VL - 351 IS - 1-2 SP - 293 EP - 307 PB - Springer CY - Dordrecht ER - TY - JOUR A1 - Hocher, Berthold A1 - Lu, Yong-Ping A1 - Reichetzeder, Christoph A1 - Zhang, Xiaoli A1 - Tsuprykov, Oleg A1 - Rahnenführer, Jan A1 - Xie, Li A1 - Li, Jian A1 - Hu, Liang A1 - Krämer, Bernhard K. A1 - Hasan, Ahmed A. T1 - Paternal eNOS deficiency in mice affects glucose homeostasis and liver glycogen in male offspring without inheritance of eNOS deficiency itself JF - Diabetologia N2 - Aims/hypothesis It was shown that maternal endothelial nitric oxide synthase (eNOS) deficiency causes fatty liver disease and numerically lower fasting glucose in female wild-type offspring, suggesting that parental genetic variants may influence the offspring's phenotype via epigenetic modifications in the offspring despite the absence of a primary genetic defect. The aim of the current study was to analyse whether paternal eNOS deficiency may cause the same phenotype as seen with maternal eNOS deficiency. Methods Heterozygous (+/-) male eNOS (Nos3) knockout mice or wild-type male mice were bred with female wild-type mice. The phenotype of wild-type offspring of heterozygous male eNOS knockout mice was compared with offspring from wild-type parents. Results Global sperm DNA methylation decreased and sperm microRNA pattern altered substantially. Fasting glucose and liver glycogen storage were increased when analysing wild-type male and female offspring of +/- eNOS fathers. Wild-type male but not female offspring of +/- eNOS fathers had increased fasting insulin and increased insulin after glucose load. Analysing candidate genes for liver fat and carbohydrate metabolism revealed that the expression of genes encoding glucocorticoid receptor (Gr; also known as Nr3c1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc1a; also known as Ppargc1a) was increased while DNA methylation of Gr exon 1A and Pgc1a promoter was decreased in the liver of male wild-type offspring of +/- eNOS fathers. The endocrine pancreas in wild-type offspring was not affected.
Conclusions/interpretation Our study suggests that paternal genetic defects such as eNOS deficiency may alter the epigenome of the sperm without transmission of the paternal genetic defect itself. In later life wild-type male offspring of +/- eNOS fathers developed increased fasting insulin and increased insulin after glucose load. These effects are associated with increased Gr and Pgc1a gene expression due to altered methylation of these genes. KW - eNOS KW - Glucocorticoid receptor KW - Insulin resistance KW - Paternal programming; KW - PGC1a Y1 - 2022 U6 - https://doi.org/10.1007/s00125-022-05700-x SN - 0012-186X SN - 1432-0428 VL - 65 IS - 7 SP - 1222 EP - 1236 PB - Springer CY - New York ER - TY - JOUR A1 - Wolf, Thomas J. A. A1 - Sanchez, David M. A1 - Yang, J. A1 - Parrish, R. M. A1 - Nunes, J. P. F. A1 - Centurion, M. A1 - Coffee, R. A1 - Cryan, J. P. A1 - Gühr, Markus A1 - Hegazy, Kareem A1 - Kirrander, Adam A1 - Li, R. K. A1 - Ruddock, J. A1 - Shen, Xiaozhe A1 - Vecchione, T. A1 - Weathersby, S. P. A1 - Weber, Peter M. A1 - Wilkin, K. A1 - Yong, Haiwang A1 - Zheng, Q. A1 - Wang, X. J. A1 - Minitti, Michael P. A1 - Martinez, Todd J. T1 - The photochemical ring-opening of 1,3-cyclohexadiene imaged by ultrafast electron diffraction JF - Nature chemistry N2 - The ultrafast photoinduced ring-opening of 1,3-cyclohexadiene constitutes a textbook example of electrocyclic reactions in organic chemistry and a model for photobiological reactions in vitamin D synthesis. Although the relaxation from the photoexcited electronic state during the ring-opening has been investigated in numerous studies, the accompanying changes in atomic distance have not been resolved. Here we present a direct and unambiguous observation of the ring-opening reaction path on the femtosecond timescale and subangstrom length scale using megaelectronvolt ultrafast electron diffraction. We followed the carbon-carbon bond dissociation and the structural opening of the 1,3-cyclohexadiene ring by the direct measurement of time-dependent changes in the distribution of interatomic distances. We observed a substantial acceleration of the ring-opening motion after internal conversion to the ground state due to a steepening of the electronic potential gradient towards the product minima. The ring-opening motion transforms into rotation of the terminal ethylene groups in the photoproduct 1,3,5-hexatriene on the subpicosecond timescale. KW - Organic chemistry KW - Photochemistry KW - Physical chemistry KW - Theoretical chemistry Y1 - 2019 U6 - https://doi.org/10.1038/s41557-019-0252-7 SN - 1755-4330 SN - 1755-4349 VL - 11 IS - 6 SP - 504 EP - 509 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Li, Huashu A1 - Liu, Xingqi A1 - Herzschuh, Ulrike A1 - Cao, Xianyong A1 - Yu, Zhitong A1 - Wang, Yong T1 - Vegetation and climate changes since the middle MIS 3 inferred from a Wulagai Lake pollen record, Inner Mongolia, Northeastern China JF - Review of palaeobotany and palynology : an international journal N2 - The climate conditions during Marine Isotope Stage (MIS) 3 were similar to present-day conditions, but whether humidity then exceeded present levels is debated, and the driving mechanisms of palaeoclimate evolution since MIS 3 remain unclear. Here, we use pollen data from Wulagai Lake, Inner Mongolia, to reconstruct vegetation and climate changes since the middle MIS 3. The steppe biome is reconstructed as the first dominant biome and the desert biome as the second, and the results show that the vegetation was steppe over the last 43,800 years. Poaceae, Artemisia, Caryophyllaceae and Humulus were abundant from middle to late MIS 3, indicating humid climate conditions. As drought-tolerant species such as Hippophae, Nitraria and Chenopodiaceae spread during MIS 2, the climate became arid. The Holocene is characterized by the dominance of steppe with mixed coniferous-broadleaved forests in the Greater Hinggan Range, and the desert biome retains high affinity scores, indicating that the climate was semi-arid. The climate from middle to late MIS 3 was wetter than in the Holocene; this shift was related to changes in the Northern Hemisphere's solar insolation and ice volume. The humid conditions during MIS 3 were attributed to strong ice–albedo feedback, which led to evaporation that was less than the precipitation. The enhanced evaporation caused by increased solar insolation and decreased ice volume might have exceeded the precipitation during the Holocene and resulted in low effective humidity in the Wulagai Lake basin. KW - Pollen KW - Biome KW - Ice volume KW - Solar insolation Y1 - 2018 U6 - https://doi.org/10.1016/j.revpalbo.2018.12.006 SN - 0034-6667 SN - 1879-0615 VL - 262 SP - 44 EP - 51 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - He, Jing A1 - Liu, Zhi-Wei A1 - Lu, Yong-Ping A1 - Li, Tao-Yuan A1 - Liang, Xu-Jing A1 - Arck, Petra A1 - Huang, Si-Min A1 - Hocher, Berthold A1 - Chen, You-Peng T1 - A systematic review and meta-analysis of influenza a virus infection during pregnancy associated with an increased risk for stillbirth and low birth weight JF - Kidney & blood pressure research : official organ of the Gesellschaft für Nephrologie ; official organ of the Deutsche Liga zur Bekämpfung des Hohen Blutdruckes e.V., Deutsche Hypertonie-Gesellschaft N2 - Background/Aims: Impaired pregnancy outcomes, such as low birth weight are associated with increased disease risk in later life, however little is known about the impact of common infectious diseases during pregnancy on birth weight. The study had two aims: a) to investigate risk factors of influenza virus infection during pregnancy, and b) to analyze the impact of influenza virus infection on pregnancy outcome, especially birth weight. Methods: Prospective and retrospective observational studies found in PubMed, MEDLINE, Embase, Google Scholar, and WangFang database were included in this meta analysis. Data of included studies was extracted and analyzed by the RevMan software. Results: Pregnant women with anemia (P=0.004, RR=1.46, 95% CI: 1.13-1.88), obesity (P<0.00001, RR=1.35, 95% CI: 1.25-1.46) and asthma (P<0.00001, RR=1.99, 95% CI: 1.67-2.37) had higher rates of influenza virus infection. Regarding birth outcomes, influenza A virus infection did not affect the likelihood for cesarean section. Mothers with influenza had a higher rate of stillbirth (P=0.04, RR=2.36, 95% CI: 1.05-5.31), and their offspring had low 5-minute APGR Scores (P=0.009, RR=1.39, 95% CI: 1.08-1.79). Furthermore, the rate for birth weight < 2500g (P=0.04, RR=1.71, 95% CI: 1.03-2.84) was increased. Conclusion: Results of this study showed that anemia, asthma and obesity during pregnancy are risk factors influenza A virus infection during pregnancy. Moreover, gestational influenza A infection impairs pregnancy outcomes and increases the risk for low birth weight, a known risk factor for later life disease susceptibility. KW - Apgar score KW - Influenza virus KW - Offspring KW - Outcome KW - Pregnancy KW - Stillbirth KW - Birth weight Y1 - 2017 U6 - https://doi.org/10.1159/000477221 SN - 1420-4096 SN - 1423-0143 VL - 42 IS - 2 SP - 232 EP - 243 PB - Karger CY - Basel ER - TY - JOUR A1 - Xu, Yong A1 - Liu, Xuemei A1 - Li, Yongge A1 - Metzler, Ralf T1 - Heterogeneous diffusion processes and nonergodicity with Gaussian colored noise in layered diffusivity landscapes JF - Physical review : E, Statistical, nonlinear and soft matter physics N2 - Heterogeneous diffusion processes (HDPs) with space-dependent diffusion coefficients D(x) are found in a number of real-world systems, such as for diffusion of macromolecules or submicron tracers in biological cells. Here, we examine HDPs in quenched-disorder systems with Gaussian colored noise (GCN) characterized by a diffusion coefficient with a power-law dependence on the particle position and with a spatially random scaling exponent. Typically, D(x) is considered to be centerd at the origin and the entire x axis is characterized by a single scaling exponent a. In this work we consider a spatially random scenario: in periodic intervals ("layers") in space D(x) is centerd to the midpoint of each interval. In each interval the scaling exponent alpha is randomly chosen from a Gaussian distribution. The effects of the variation of the scaling exponents, the periodicity of the domains ("layer thickness") of the diffusion coefficient in this stratified system, and the correlation time of the GCN are analyzed numerically in detail. We discuss the regimes of superdiffusion, subdiffusion, and normal diffusion realisable in this system. We observe and quantify the domains where nonergodic and non-Gaussian behaviors emerge in this system. Our results provide new insights into the understanding of weak ergodicity breaking for HDPs driven by colored noise, with potential applications in quenched layered systems, typical model systems for diffusion in biological cells and tissues, as well as for diffusion in geophysical systems. Y1 - 2020 U6 - https://doi.org/10.1103/PhysRevE.102.062106 SN - 2470-0045 SN - 2470-0053 VL - 102 IS - 6 PB - American Physical Society CY - College Park ER - TY - GEN A1 - Li, Yongge A1 - Mei, Ruoxing A1 - Xu, Yong A1 - Kurths, Jürgen A1 - Duan, Jinqiao A1 - Metzler, Ralf T1 - Particle dynamics and transport enhancement in a confined channel with position-dependent diffusivity T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - This work focuses on the dynamics of particles in a confined geometry with position-dependent diffusivity, where the confinement is modelled by a periodic channel consisting of unit cells connected by narrow passage ways. We consider three functional forms for the diffusivity, corresponding to the scenarios of a constant (D ₀), as well as a low (D ₘ) and a high (D d) mobility diffusion in cell centre of the longitudinally symmetric cells. Due to the interaction among the diffusivity, channel shape and external force, the system exhibits complex and interesting phenomena. By calculating the probability density function, mean velocity and mean first exit time with the Itô calculus form, we find that in the absence of external forces the diffusivity D d will redistribute particles near the channel wall, while the diffusivity D ₘ will trap them near the cell centre. The superposition of external forces will break their static distributions. Besides, our results demonstrate that for the diffusivity D d, a high dependence on the x coordinate (parallel with the central channel line) will improve the mean velocity of the particles. In contrast, for the diffusivity D ₘ, a weak dependence on the x coordinate will dramatically accelerate the moving speed. In addition, it shows that a large external force can weaken the influences of different diffusivities; inversely, for a small external force, the types of diffusivity affect significantly the particle dynamics. In practice, one can apply these results to achieve a prominent enhancement of the particle transport in two- or three-dimensional channels by modulating the local tracer diffusivity via an engineered gel of varying porosity or by adding a cold tube to cool down the diffusivity along the central line, which may be a relevant effect in engineering applications. Effects of different stochastic calculi in the evaluation of the underlying multiplicative stochastic equation for different physical scenarios are discussed. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 974 KW - diffusion KW - channel KW - space-dependent diffusivity Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-474542 SN - 1866-8372 IS - 974 ER - TY - JOUR A1 - Li, Yongge A1 - Mei, Ruoxing A1 - Xu, Yong A1 - Kurths, Jürgen A1 - Duan, Jinqiao A1 - Metzler, Ralf T1 - Particle dynamics and transport enhancement in a confined channel with position-dependent diffusivity JF - New Journal of Physics N2 - This work focuses on the dynamics of particles in a confined geometry with position-dependent diffusivity, where the confinement is modelled by a periodic channel consisting of unit cells connected by narrow passage ways. We consider three functional forms for the diffusivity, corresponding to the scenarios of a constant (D ₀), as well as a low (D ₘ) and a high (D d) mobility diffusion in cell centre of the longitudinally symmetric cells. Due to the interaction among the diffusivity, channel shape and external force, the system exhibits complex and interesting phenomena. By calculating the probability density function, mean velocity and mean first exit time with the Itô calculus form, we find that in the absence of external forces the diffusivity D d will redistribute particles near the channel wall, while the diffusivity D ₘ will trap them near the cell centre. The superposition of external forces will break their static distributions. Besides, our results demonstrate that for the diffusivity D d, a high dependence on the x coordinate (parallel with the central channel line) will improve the mean velocity of the particles. In contrast, for the diffusivity D ₘ, a weak dependence on the x coordinate will dramatically accelerate the moving speed. In addition, it shows that a large external force can weaken the influences of different diffusivities; inversely, for a small external force, the types of diffusivity affect significantly the particle dynamics. In practice, one can apply these results to achieve a prominent enhancement of the particle transport in two- or three-dimensional channels by modulating the local tracer diffusivity via an engineered gel of varying porosity or by adding a cold tube to cool down the diffusivity along the central line, which may be a relevant effect in engineering applications. Effects of different stochastic calculi in the evaluation of the underlying multiplicative stochastic equation for different physical scenarios are discussed. KW - diffusion KW - channel KW - space-dependent diffusivity Y1 - 2020 U6 - https://doi.org/10.1088/1367-2630/ab81b9 SN - 1367-2630 VL - 22 PB - Dt. Physikalische Ges. CY - Bad Honnef ER - TY - JOUR A1 - Mutothya, Nicholas Mwilu A1 - Xu, Yong A1 - Li, Yongge A1 - Metzler, Ralf T1 - Characterising stochastic motion in heterogeneous media driven by coloured non-Gaussian noise JF - Journal of physics : A, Mathematical and theoretical N2 - We study the stochastic motion of a test particle in a heterogeneous medium in terms of a position dependent diffusion coefficient mimicking measured deterministic diffusivity gradients in biological cells or the inherent heterogeneity of geophysical systems. Compared to previous studies we here investigate the effect of the interplay of anomalous diffusion effected by position dependent diffusion coefficients and coloured non-Gaussian noise. The latter is chosen to be distributed according to Tsallis' q-distribution, representing a popular example for a non-extensive statistic. We obtain the ensemble and time averaged mean squared displacements for this generalised process and establish its non-ergodic properties as well as analyse the non-Gaussian nature of the associated displacement distribution. We consider both non-stratified and stratified environments. KW - diffusion KW - anomalous diffusion KW - non-extensive statistics KW - coloured KW - noise KW - heterogeneous diffusion process Y1 - 2021 U6 - https://doi.org/10.1088/1751-8121/abfba6 SN - 1751-8113 SN - 1751-8121 VL - 54 IS - 29 PB - IOP Publ. Ltd. CY - Bristol ER - TY - JOUR A1 - Pavlyukevich, Ilya A1 - Li, Yongge A1 - Xu, Yong A1 - Chechkin, Aleksei V. T1 - Directed transport induced by spatially modulated Levy flights JF - Journal of physics : A, Mathematical and theoretical N2 - In this paper we study the dynamics of a particle in a ratchet potential subject to multiplicative alpha-stable Levy noise, alpha is an element of(0, 2), in the limit of a noise amplitude epsilon -> 0. We compare the dynamics for Ito and Marcus multiplicative noises and obtain the explicit asymptotics of the escape time in the wells and transition probabilities between the wells. A detailed analysis of the noise-induced current is performed for the Seebeck ratchet with a weak multiplicative noise for alpha is an element of(0, 2]. KW - Levy flights KW - multiplicative noise KW - Seebeck ratchet KW - directed transport Y1 - 2015 U6 - https://doi.org/10.1088/1751-8113/48/49/495004 SN - 1751-8113 SN - 1751-8121 VL - 48 IS - 49 PB - IOP Publ. Ltd. CY - Bristol ER - TY - JOUR A1 - Liang, Xu-Jing A1 - Huang, Si-Min A1 - Li, Jian-Ping A1 - Zhu, Xian-Nv A1 - Lu, Yong-Ping A1 - Hocher, Berthold A1 - Chen, You-Peng T1 - Hepatic impairment induced by scrub typhus is associated with new onset of renal dysfunction JF - Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion N2 - Background: Scrub typhus is a potentially fatal infectious disease caused by Orientia tsutsugamushi. There is little attention given to hepatic impairment in the adults with scrub typhus. This study investigated the incidence and the prognostic implications of hepatic impairment in patients with scrub typhus. Methods: We retrospectively reviewed a total of 143 adult patients with scrub typhus who were admitted between January 1999 and December 2010 in Guangdong province, China. The patients were divided into three groups, e.g., normal, mild, and moderate to severe groups based on the elevated serum ALT and/or total bilirubin levels. Furthermore, clinical characteristics and prognosis of the patient groups were compared. Results: 109 patients (76.2%) had abnormal liver function. Among the patients with hepatic impairment 45 cases (31.4%), 54 cases (37.8%), and 10 cases (7.0%) had mild, moderate, and severe hepatic damage, respectively. The moderate to severe hepatic impairment group had higher levels of serum creatinine compared with that of normal hepatic function. The incidence of new onset of renal dysfunction - defined as peak serum creatinine >= 176 mu mol/L during hospital stay with no evidence of renal disease prior hospitalization - was 0% in the mild hepatic impairment group, 8.9% in the moderate hepatic impairment group, and 21.9% in the severe hepatic impairment group, (p = 0.005 for trend). Additionally, the patients with hepatic impairment (n = 109) had higher incidences of episodes of thrombocytopenia (45.9% vs. 8.82%, p < 0.001), hypoalbuminemia (50.5% vs. 11.8%, p < 0.001), new onset of renal dysfunction (16.5% vs. 0.0%, p = 0.011), and electrocardiogram abnormality (28.4% vs. 8.82%, p = 0.019) than the patients without hepatic impairment. Conclusions: The degree of hepatic impairment induced by scrub typhus is associated with new onset of renal dysfunction. KW - hepatic impairment KW - renal dysfunction KW - complication KW - outcome KW - scrub typhus Y1 - 2014 U6 - https://doi.org/10.7754/Clin.Lab.2013.121203 SN - 1433-6510 VL - 60 IS - 1 SP - 63 EP - 68 PB - Clin Lab Publ., Verl. Klinisches Labor CY - Heidelberg ER - TY - JOUR A1 - Lu, Yong-Ping A1 - Lung, Xu-Jing A1 - Xiao, Xiao-Min A1 - Huang, Si-Min A1 - Liu, Zhi-Wei A1 - Li, Jian A1 - Hocher, Berthold A1 - Chen, You-Peng T1 - Telbivudine during the second and third trimester of pregnancy interrupts HBV intrauterine transmission: a systematic review and meta-analysis JF - Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion N2 - Beckground: Evaluate the efficacy and safety of telbivudine during the 2nd and 3rd trimester of pregnancy in intrauterine transmission of hepatitis B virus (HBV). Based on the principle of Cochrane systematic reviews, a database was constructed from Medline, EMBASE, Cochrane Library, the US National Science Digital Library (NSDL), the China Biological Medicine Database (CBM-disc), and contact with Chinese experts in the field from November 2006 to February 2013. Results: Either the Mantel-Haenszel or Inverse Variance fixed-effects model or Mantel-Haenszel or Inverse Variance random-effects model was applied for all analyses indicated by odds ratio (OR) and 95% confidence interval (CI). The meta-analysis based on new onset of HBsAg seropositivity of infants at 6 - 12 months postpartum revealed that the control group had an intrauterine transmission rate of 8.25 - 42.31%. This rate was reduced to 0 - 14.29% in the telbivudine treatment group (OR 0.09, 95% CI 0.04 - 0.22, including seven trials, p < 0.001). The rates of intrauterine transmission based on new onset of HBV DNA seropositivity of infants at 6 - 12 months postpartum were 8.25 - 19.23% in the control group and 0 - 3.57% in the treatment group (OR 0.07, 95% CI 0.02 - 0.22, p < 0.001, including only five trials, since two trials had no data on HBV DNA in infants). With the exception of CK elevations, adverse effect frequencies were similar in both groups. Conclusions: Telbivudine is an effective and safe drug for preventing intrauterine transmission of HBV. KW - telbivudine KW - meta-analysis KW - intrauterine KW - transmission of hepatitis B virus (HBV) KW - clinical studies KW - safety efficacy Y1 - 2014 U6 - https://doi.org/10.7754/Clin.Lab.2013.130408 SN - 1433-6510 VL - 60 IS - 4 SP - 571 EP - 586 PB - Clin Lab Publ., Verl. Klinisches Labor CY - Heidelberg ER - TY - JOUR A1 - Li, Jian A1 - Chen, You-Peng A1 - Dong, Yun-Peng A1 - Yu, Cal-Hong A1 - Lu, Yong-Ping A1 - Xiao, Xiao-Min A1 - Hocher, Berthold T1 - The impact of umbilical blood flow regulation on fetal development differs in diabetic and non-diabetic pregnancy JF - Kidney & blood pressure research : official organ of the Gesellschaft für Nephrologie N2 - Background/Aims: Diabetes is well-known to influence endothelial function. Endothelial function and blood flow regulation might be different in diabetic and non-diabetic pregnancy. However, the impact of umbilical blood flow regulation in gestational diabetes on fetal development is unknown so far. Methods: In a prospective birth cohort study, we analyzed the association of the umbilical artery Doppler indices (pulsatility index, resistance index and systolic/diastolic ratio) and fetal size measures (biparietal diameter, head circumference, abdominal circumference, femur length and birth weight) in 519 non-gestational diabetes mellitus pregnancies (controls) and 226 gestational diabetes mellitus pregnancies in middle (day 160.32 +/- 16.29 of gestation) and late (day 268.12 +/- 13.04 of gestation) pregnancy. Results: Multiple regression analysis considering confounding factors (gestational day of ultrasound examination, offspring sex, maternal body mess index before pregnancy, maternal age at delivery, maternal body weight at delivery and maternal hypertension) showed that umbilical artery Doppler indices (pulsatility index, resistance index and systolic/diastolic ratio) were associated with fetal head circumference and femur length in middle gestational diabetes mellitus pregnancy but not in non-gestational diabetes mellitus pregnancy. Head circumference, biparietal diameter, abdominal circumference and femur length in mid gestation were smaller in fetus of gestational diabetes mellitus pregnancy versus non-gestational diabetes mellitus pregnancy. In contrast to non-gestational diabetes mellitus pregnancy in late gestation, umbilical artery Doppler indices in gestational diabetes mellitus pregnancy were not associated with ultrasound measures of fetal growth. Birth weight was slightly increased in gestational diabetes mellitus pregnancy as compared to non-gestational diabetes mellitus pregnancy. Conclusions: The impact of umbilical blood flow on fetal growth is time dependent in human gestational diabetes mellitus and non-gestational diabetes mellitus pregnancy. In gestational diabetes mellitus pregnancy umbilical blood flow is critical for organ development in much earlier stages of pregnancy as compared to non-gestational diabetes mellitus pregnancy. The physiological and molecular pathways why there is a catch up growth in later times of gestational diabetes mellitus pregnancy resulting in larger gestational diabetes mellitus babies at birth needs to be addressed in further studies. KW - Umbilical artery Doppler KW - Blood flow resistance KW - Gestational diabetes mellitus KW - Fetal development Y1 - 2014 U6 - https://doi.org/10.1159/000355815 SN - 1420-4096 SN - 1423-0143 VL - 39 IS - 4 SP - 369 EP - 377 PB - Karger CY - Basel ER - TY - JOUR A1 - Chen, You-Peng A1 - Lu, Yong-Ping A1 - Li, Jian A1 - Liu, Zhi-Wei A1 - Chen, Wen-Jing A1 - Liang, Xu-Jing A1 - Chen, Xin A1 - Wen, Wang-Rong A1 - Xiao, Xiao-Min A1 - Reichetzeder, Christoph A1 - Hocher, Berthold T1 - Fetal and maternal angiotensin (1-7) are associated with preterm birth JF - Journal of hypertension N2 - Background: Recent studies show that preterm birth is associated with hypertension in later life. The renin-angiotensin system (RAS) during pregnancy influences fetal growth and development. In the current study, we investigated the impact of fetal as well as maternal angiotensin (1-7) [Ang (1-7)] and angiotensin II (Ang II) plasma concentrations on the risk of preterm birth. Methods: Three hundred and nine pregnant women were prospectively included into the study. The pregnant women were divided into two groups, for example, preterm birth of lower than 37 gestational weeks (n = 17) and full-term birth of 37 gestational weeks or more (n = 292). Maternal and neonatal plasma Ang (1-7) and Ang II concentrations were analyzed at birth from maternal venous blood and umbilical cord blood, respectively. Risk factors for premature birth were determined by multiple logistic regression analysis. Results: Fetal and maternal plasma Ang (1-7) concentrations in the preterm group were lower than those of the term group fetal Ang (1-7) preterm birth: 486.15 +/- 337.34 ng/l and fetal Ang (1-7) term birth: 833.84 +/- 698.12 ng/l and maternal Ang (1-7) preterm birth: 399.86 +/- 218.93 ng/l; maternal Ang (1-7) term birth: 710.34 +/- 598.22 ng/l. Multiple logistic regression analysis considering confounding factors revealed that preeclampsia (P < 0.001), premature rupture of membranes (P = 0.001), lower concentration of maternal Ang (1-7) (P = 0.013) and fetal plasma Ang (1-7) (P = 0.032) were independently associated with preterm birth. We could furthermore demonstrate that the maternal Ang (1-7)/Ang II ratio is independently associated with gestational hypertension or preeclampsia, factors causing preterm birth. Conclusions: Lower concentrations of maternal and fetal Ang (1-7) are independently associated with preterm birth - a risk factor of hypertension in later life. KW - angiotensin (1-7) KW - angiotensin II KW - cardiovascular disease KW - fetal programming KW - intrauterine fetal growth KW - pregnancy KW - preterm delivery Y1 - 2014 U6 - https://doi.org/10.1097/HJH.0000000000000251 SN - 0263-6352 SN - 1473-5598 VL - 32 IS - 9 SP - 1833 EP - 1841 PB - Lippincott Williams & Wilkins CY - Philadelphia ER - TY - JOUR A1 - Li, Jian A1 - Lu, Yong Ping A1 - Reichetzeder, Christoph A1 - Kalk, Philipp A1 - Kleuser, Burkhard A1 - Adamski, Jerzy A1 - Hocher, Berthold T1 - Maternal PCaaC38:6 is Associated With Preterm Birth - a Risk Factor for Early and Late Adverse Outcome of the Offspring JF - Journal of European public policy N2 - Background/Aims: Preterm birth (PTB) and low birth weight (LBW) significantly influence mortality and morbidity of the offspring in early life and also have long-term consequences in later life. A better understanding of the molecular mechanisms of preterm birth could provide new insights regarding putative preventive strategies. Metabolomics provides a powerful analytic tool to readout complex interactions between genetics, environment and health and may serve to identify relevant biomarkers. In this study, the association between 163 targeted maternal blood metabolites and gestational age was investigated in order to find candidate biomarkers for PTB. Methods: Five hundred twenty-three women were included into this observational study. Maternal blood was obtained before delivery. The concentration of 163 maternal serum metabolites was measured by flow injection tandem mass spectrometry. To find putative biomarkers for preterm birth, a three-step analysis was designed: bivariate correlation analysis followed by multivariable regression analysis and a comparison of mean values among gestational age groups. Results: Bivariate correlation analysis showed that 2 acylcarnitines (C16:2, C2), 1 amino acids (xLeu), 8 diacyl-PCs (PCaaC36:4, PCaaC38:4, PCaaC38:5, PCaaC38:6, PCaaC40:4, PCaaC40:5, PCaaC40:6, PCaaC42:4), and 1 Acylalkyl-PCs (PCaeC40:5) were inversely correlated with gestational age. Multivariable regression analysis confounded for PTB history, maternal body mass index (BMI) before pregnancy, systolic blood pressure at the third trimester, and maternal body weight at the third trimester, showed that the diacyl-PC PCaaC38:6 was the only metabolite inversely correlated with gestational age. Conclusions: Maternal blood concentrations of PCaaC38:6 are independently associated with gestational age. (C) 2016 The Author(s) Published by S. Karger AG, Basel KW - Metabolomics KW - PCaaC38:6 KW - Biomarker KW - Preterm birth Y1 - 2016 U6 - https://doi.org/10.1159/000443428 SN - 1420-4096 SN - 1423-0143 VL - 41 SP - 250 EP - 257 PB - Karger CY - Basel ER -