TY  - JOUR
A1  - Taal, H. Rob
A1  - St Pourcain, Beate
A1  - Thiering, Elisabeth
A1  - Das, Shikta
A1  - Mook-Kanamori, Dennis O.
A1  - Warrington, Nicole M.
A1  - Kaakinen, Marika
A1  - Kreiner-Moller, Eskil
A1  - Bradfield, Jonathan P.
A1  - Freathy, Rachel M.
A1  - Geller, Frank
A1  - Guxens, Monica
A1  - Cousminer, Diana L.
A1  - Kerkhof, Marjan
A1  - Timpson, Nicholas J.
A1  - Ikram, M. Arfan
A1  - Beilin, Lawrence J.
A1  - Bonnelykke, Klaus
A1  - Buxton, Jessica L.
A1  - Charoen, Pimphen
A1  - Chawes, Bo Lund Krogsgaard
A1  - Eriksson, Johan
A1  - Evans, David M.
A1  - Hofman, Albert
A1  - Kemp, John P.
A1  - Kim, Cecilia E.
A1  - Klopp, Norman
A1  - Lahti, Jari
A1  - Lye, Stephen J.
A1  - McMahon, George
A1  - Mentch, Frank D.
A1  - Mueller-Nurasyid, Martina
A1  - O'Reilly, Paul F.
A1  - Prokopenko, Inga
A1  - Rivadeneira, Fernando
A1  - Steegers, Eric A. P.
A1  - Sunyer, Jordi
A1  - Tiesler, Carla
A1  - Yaghootkar, Hanieh
A1  - Breteler, Monique M. B.
A1  - Debette, Stephanie
A1  - Fornage, Myriam
A1  - Gudnason, Vilmundur
A1  - Launer, Lenore J.
A1  - van der Lugt, Aad
A1  - Mosley, Thomas H.
A1  - Seshadri, Sudha
A1  - Smith, Albert V.
A1  - Vernooij, Meike W.
A1  - Blakemore, Alexandra I. F.
A1  - Chiavacci, Rosetta M.
A1  - Feenstra, Bjarke
A1  - Fernandez-Banet, Julio
A1  - Grant, Struan F. A.
A1  - Hartikainen, Anna-Liisa
A1  - van der Heijden, Albert J.
A1  - Iniguez, Carmen
A1  - Lathrop, Mark
A1  - McArdle, Wendy L.
A1  - Molgaard, Anne
A1  - Newnham, John P.
A1  - Palmer, Lyle J.
A1  - Palotie, Aarno
A1  - Pouta, Annneli
A1  - Ring, Susan M.
A1  - Sovio, Ulla
A1  - Standl, Marie
A1  - Uitterlinden, Andre G.
A1  - Wichmann, H-Erich
A1  - Vissing, Nadja Hawwa
A1  - DeCarli, Charles
A1  - van Duijn, Cornelia M.
A1  - McCarthy, Mark I.
A1  - Koppelman, Gerard H.
A1  - Estivill, Xavier
A1  - Hattersley, Andrew T.
A1  - Melbye, Mads
A1  - Bisgaard, Hans
A1  - Pennell, Craig E.
A1  - Widen, Elisabeth
A1  - Hakonarson, Hakon
A1  - Smith, George Davey
A1  - Heinrich, Joachim
A1  - Jarvelin, Marjo-Riitta
A1  - Jaddoe, Vincent W. V.
A1  - Adair, Linda S.
A1  - Ang, Wei
A1  - Atalay, Mustafa
A1  - van Beijsterveldt, Toos
A1  - Bergen, Nienke
A1  - Benke, Kelly
A1  - Berry, Diane J.
A1  - Bradfield, Jonathan P.
A1  - Charoen, Pimphen
A1  - Coin, Lachlan
A1  - Cousminer, Diana L.
A1  - Das, Shikta
A1  - Davis, Oliver S. P.
A1  - Elliott, Paul
A1  - Evans, David M.
A1  - Feenstra, Bjarke
A1  - Flexeder, Claudia
A1  - Frayling, Tim
A1  - Freathy, Rachel M.
A1  - Gaillard, Romy
A1  - Geller, Frank
A1  - Groen-Blokhuis, Maria
A1  - Goh, Liang-Kee
A1  - Guxens, Monica
A1  - Haworth, Claire M. A.
A1  - Hadley, Dexter
A1  - Hebebrand, Johannes
A1  - Hinney, Anke
A1  - Hirschhorn, Joel N.
A1  - Holloway, John W.
A1  - Holst, Claus
A1  - Hottenga, Jouke Jan
A1  - Horikoshi, Momoko
A1  - Huikari, Ville
A1  - Hypponen, Elina
A1  - Iniguez, Carmen
A1  - Kaakinen, Marika
A1  - Kilpelainen, Tuomas O.
A1  - Kirin, Mirna
A1  - Kowgier, Matthew
A1  - Lakka, Hanna-Maaria
A1  - Lange, Leslie A.
A1  - Lawlor, Debbie A.
A1  - Lehtimaki, Terho
A1  - Lewin, Alex
A1  - Lindgren, Cecilia
A1  - Lindi, Virpi
A1  - Maggi, Reedik
A1  - Marsh, Julie
A1  - Middeldorp, Christel
A1  - Millwood, Iona
A1  - Mook-Kanamori, Dennis O.
A1  - Murray, Jeffrey C.
A1  - Nivard, Michel
A1  - Nohr, Ellen Aagaard
A1  - Ntalla, Ioanna
A1  - Oken, Emily
A1  - O'Reilly, Paul F.
A1  - Palmer, Lyle J.
A1  - Panoutsopoulou, Kalliope
A1  - Pararajasingham, Jennifer
A1  - Prokopenko, Inga
A1  - Rodriguez, Alina
A1  - Salem, Rany M.
A1  - Sebert, Sylvain
A1  - Siitonen, Niina
A1  - Sovio, Ulla
A1  - St Pourcain, Beate
A1  - Strachan, David P.
A1  - Sunyer, Jordi
A1  - Taal, H. Rob
A1  - Teo, Yik-Ying
A1  - Thiering, Elisabeth
A1  - Tiesler, Carla
A1  - Uitterlinden, Andre G.
A1  - Valcarcel, Beatriz
A1  - Warrington, Nicole M.
A1  - White, Scott
A1  - Willemsen, Gonneke
A1  - Yaghootkar, Hanieh
A1  - Zeggini, Eleftheria
A1  - Boomsma, Dorret I.
A1  - Cooper, Cyrus
A1  - Estivill, Xavier
A1  - Gillman, Matthew
A1  - Grant, Struan F. A.
A1  - Hakonarson, Hakon
A1  - Hattersley, Andrew T.
A1  - Heinrich, Joachim
A1  - Hocher, Berthold
A1  - Jaddoe, Vincent W. V.
A1  - Jarvelin, Marjo-Riitta
A1  - Lakka, Timo A.
A1  - McCarthy, Mark I.
A1  - Melbye, Mads
A1  - Mohlke, Karen L.
A1  - Dedoussis, George V.
A1  - Ong, Ken K.
A1  - Pearson, Ewan R.
A1  - Pennell, Craig E.
A1  - Price, Thomas S.
A1  - Power, Chris
A1  - Raitakari, Olli T.
A1  - Saw, Seang-Mei
A1  - Scherag, Andre
A1  - Simell, Olli
A1  - Sorensen, Thorkild I. A.
A1  - Timpson, Nicholas J.
A1  - Widen, Elisabeth
A1  - Wilson, James F.
A1  - Ang, Wei
A1  - van Beijsterveldt, Toos
A1  - Bergen, Nienke
A1  - Benke, Kelly
A1  - Berry, Diane J.
A1  - Bradfield, Jonathan P.
A1  - Charoen, Pimphen
A1  - Coin, Lachlan
A1  - Cousminer, Diana L.
A1  - Das, Shikta
A1  - Elliott, Paul
A1  - Evans, David M.
A1  - Frayling, Tim
A1  - Freathy, Rachel M.
A1  - Gaillard, Romy
A1  - Groen-Blokhuis, Maria
A1  - Guxens, Monica
A1  - Hadley, Dexter
A1  - Hottenga, Jouke Jan
A1  - Huikari, Ville
A1  - Hypponen, Elina
A1  - Kaakinen, Marika
A1  - Kowgier, Matthew
A1  - Lawlor, Debbie A.
A1  - Lewin, Alex
A1  - Lindgren, Cecilia
A1  - Marsh, Julie
A1  - Middeldorp, Christel
A1  - Millwood, Iona
A1  - Mook-Kanamori, Dennis O.
A1  - Nivard, Michel
A1  - O'Reilly, Paul F.
A1  - Palmer, Lyle J.
A1  - Prokopenko, Inga
A1  - Rodriguez, Alina
A1  - Sebert, Sylvain
A1  - Sovio, Ulla
A1  - St Pourcain, Beate
A1  - Standl, Marie
A1  - Strachan, David P.
A1  - Sunyer, Jordi
A1  - Taal, H. Rob
A1  - Thiering, Elisabeth
A1  - Tiesler, Carla
A1  - Uitterlinden, Andre G.
A1  - Valcarcel, Beatriz
A1  - Warrington, Nicole M.
A1  - White, Scott
A1  - Willemsen, Gonneke
A1  - Yaghootkar, Hanieh
A1  - Boomsma, Dorret I.
A1  - Estivill, Xavier
A1  - Grant, Struan F. A.
A1  - Hakonarson, Hakon
A1  - Hattersley, Andrew T.
A1  - Heinrich, Joachim
A1  - Jaddoe, Vincent W. V.
A1  - Jarvelin, Marjo-Riitta
A1  - McCarthy, Mark I.
A1  - Pennell, Craig E.
A1  - Power, Chris
A1  - Timpson, Nicholas J.
A1  - Widen, Elisabeth
A1  - Ikram, M. Arfan
A1  - Fornage, Myriam
A1  - Smith, Albert V.
A1  - Seshadri, Sudha
A1  - Schmidt, Reinhold
A1  - Debette, Stephanie
A1  - Vrooman, Henri A.
A1  - Sigurdsson, Sigurdur
A1  - Ropele, Stefan
A1  - Coker, Laura H.
A1  - Longstreth, W. T.
A1  - Niessen, Wiro J.
A1  - DeStefano, Anita L.
A1  - Beiser, Alexa
A1  - Zijdenbos, Alex P.
A1  - Struchalin, Maksim
A1  - Jack, Clifford R.
A1  - Nalls, Mike A.
A1  - Au, Rhoda
A1  - Hofman, Albert
A1  - Gudnason, Haukur
A1  - van der Lugt, Aad
A1  - Harris, Tamara B.
A1  - Meeks, William M.
A1  - Vernooij, Meike W.
A1  - van Buchem, Mark A.
A1  - Catellier, Diane
A1  - Gudnason, Vilmundur
A1  - Windham, B. Gwen
A1  - Wolf, Philip A.
A1  - van Duijn, Cornelia M.
A1  - Mosley, Thomas H.
A1  - Schmidt, Helena
A1  - Launer, Lenore J.
A1  - Breteler, Monique M. B.
A1  - DeCarli, Charles
T1  - Common variants at 12q15 and 12q24 are associated with infant head circumference
JF  - Nature genetics
N2  - To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association studies (GWAS) (N = 10,768 individuals of European ancestry enrolled in pregnancy and/or birth cohorts) and followed up three lead signals in six replication studies (combined N = 19,089). rs7980687 on chromosome 12q24 (P = 8.1 x 10(-9)) and rs1042725 on chromosome 12q15 (P = 2.8 x 10(-10)) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height(1), their effects on infant head circumference were largely independent of height (P = 3.8 x 10(-7) for rs7980687 and P = 1.3 x 10(-7) for rs1042725 after adjustment for infant height). A third signal, rs11655470 on chromosome 17q21, showed suggestive evidence of association with head circumference (P = 3.9 x 10(-6)). SNPs correlated to the 17q21 signal have shown genome-wide association with adult intracranial volume(2), Parkinson's disease and other neurodegenerative diseases(3-5), indicating that a common genetic variant in this region might link early brain growth with neurological disease in later life.
Y1  - 2012
U6  - https://doi.org/10.1038/ng.2238
SN  - 1061-4036
VL  - 44
IS  - 5
SP  - 532
EP  - +
PB  - Nature Publ. Group
CY  - New York
ER  - 
TY  - JOUR
A1  - Middeldorp, Christel M.
A1  - Mahajan, Anubha
A1  - Horikoshi, Momoko
A1  - Robertson, Neil R.
A1  - Beaumont, Robin N.
A1  - Bradfield, Jonathan P.
A1  - Bustamante, Mariona
A1  - Cousminer, Diana L.
A1  - Day, Felix R.
A1  - De Silva, N. Maneka
A1  - Guxens, Monica
A1  - Mook-Kanamori, Dennis O.
A1  - St Pourcain, Beate
A1  - Warrington, Nicole M.
A1  - Adair, Linda S.
A1  - Ahlqvist, Emma
A1  - Ahluwalia, Tarunveer Singh
A1  - Almgren, Peter
A1  - Ang, Wei
A1  - Atalay, Mustafa
A1  - Auvinen, Juha
A1  - Bartels, Meike
A1  - Beckmann, Jacques S.
A1  - Bilbao, Jose Ramon
A1  - Bond, Tom
A1  - Borja, Judith B.
A1  - Cavadino, Alana
A1  - Charoen, Pimphen
A1  - Chen, Zhanghua
A1  - Coin, Lachlan
A1  - Cooper, Cyrus
A1  - Curtin, John A.
A1  - Custovic, Adnan
A1  - Das, Shikta
A1  - Davies, Gareth E.
A1  - Dedoussis, George V.
A1  - Duijts, Liesbeth
A1  - Eastwood, Peter R.
A1  - Eliasen, Anders U.
A1  - Elliott, Paul
A1  - Eriksson, Johan G.
A1  - Estivill, Xavier
A1  - Fadista, Joao
A1  - Fedko, Iryna O.
A1  - Frayling, Timothy M.
A1  - Gaillard, Romy
A1  - Gauderman, W. James
A1  - Geller, Frank
A1  - Gilliland, Frank
A1  - Gilsanz, Vincente
A1  - Granell, Raquel
A1  - Grarup, Niels
A1  - Groop, Leif
A1  - Hadley, Dexter
A1  - Hakonarson, Hakon
A1  - Hansen, Torben
A1  - Hartman, Catharina A.
A1  - Hattersley, Andrew T.
A1  - Hayes, M. Geoffrey
A1  - Hebebrand, Johannes
A1  - Heinrich, Joachim
A1  - Helgeland, Oyvind
A1  - Henders, Anjali K.
A1  - Henderson, John
A1  - Henriksen, Tine B.
A1  - Hirschhorn, Joel N.
A1  - Hivert, Marie-France
A1  - Hocher, Berthold
A1  - Holloway, John W.
A1  - Holt, Patrick
A1  - Hottenga, Jouke-Jan
A1  - Hypponen, Elina
A1  - Iniguez, Carmen
A1  - Johansson, Stefan
A1  - Jugessur, Astanand
A1  - Kahonen, Mika
A1  - Kalkwarf, Heidi J.
A1  - Kaprio, Jaakko
A1  - Karhunen, Ville
A1  - Kemp, John P.
A1  - Kerkhof, Marjan
A1  - Koppelman, Gerard H.
A1  - Korner, Antje
A1  - Kotecha, Sailesh
A1  - Kreiner-Moller, Eskil
A1  - Kulohoma, Benard
A1  - Kumar, Ashish
A1  - Kutalik, Zoltan
A1  - Lahti, Jari
A1  - Lappe, Joan M.
A1  - Larsson, Henrik
A1  - Lehtimaki, Terho
A1  - Lewin, Alexandra M.
A1  - Li, Jin
A1  - Lichtenstein, Paul
A1  - Lindgren, Cecilia M.
A1  - Lindi, Virpi
A1  - Linneberg, Allan
A1  - Liu, Xueping
A1  - Liu, Jun
A1  - Lowe, William L.
A1  - Lundstrom, Sebastian
A1  - Lyytikainen, Leo-Pekka
A1  - Ma, Ronald C. W.
A1  - Mace, Aurelien
A1  - Magi, Reedik
A1  - Magnus, Per
A1  - Mamun, Abdullah A.
A1  - Mannikko, Minna
A1  - Martin, Nicholas G.
A1  - Mbarek, Hamdi
A1  - McCarthy, Nina S.
A1  - Medland, Sarah E.
A1  - Melbye, Mads
A1  - Melen, Erik
A1  - Mohlke, Karen L.
A1  - Monnereau, Claire
A1  - Morgen, Camilla S.
A1  - Morris, Andrew P.
A1  - Murray, Jeffrey C.
A1  - Myhre, Ronny
A1  - Najman, Jackob M.
A1  - Nivard, Michel G.
A1  - Nohr, Ellen A.
A1  - Nolte, Ilja M.
A1  - Ntalla, Ioanna
A1  - Oberfield, Sharon E.
A1  - Oken, Emily
A1  - Oldehinkel, Albertine J.
A1  - Pahkala, Katja
A1  - Palviainen, Teemu
A1  - Panoutsopoulou, Kalliope
A1  - Pedersen, Oluf
A1  - Pennell, Craig E.
A1  - Pershagen, Goran
A1  - Pitkanen, Niina
A1  - Plomin, Robert
A1  - Power, Christine
A1  - Prasad, Rashmi B.
A1  - Prokopenko, Inga
A1  - Pulkkinen, Lea
A1  - Raikkonen, Katri
A1  - Raitakari, Olli T.
A1  - Reynolds, Rebecca M.
A1  - Richmond, Rebecca C.
A1  - Rivadeneira, Fernando
A1  - Rodriguez, Alina
A1  - Rose, Richard J.
A1  - Salem, Rany
A1  - Santa-Marina, Loreto
A1  - Saw, Seang-Mei
A1  - Schnurr, Theresia M.
A1  - Scott, James G.
A1  - Selzam, Saskia
A1  - Shepherd, John A.
A1  - Simpson, Angela
A1  - Skotte, Line
A1  - Sleiman, Patrick M. A.
A1  - Snieder, Harold
A1  - Sorensen, Thorkild I. A.
A1  - Standl, Marie
A1  - Steegers, Eric A. P.
A1  - Strachan, David P.
A1  - Straker, Leon
A1  - Strandberg, Timo
A1  - Taylor, Michelle
A1  - Teo, Yik-Ying
A1  - Thiering, Elisabeth
A1  - Torrent, Maties
A1  - Tyrrell, Jessica
A1  - Uitterlinden, Andre G.
A1  - van Beijsterveldt, Toos
A1  - van der Most, Peter J.
A1  - van Duijn, Cornelia M.
A1  - Viikari, Jorma
A1  - Vilor-Tejedor, Natalia
A1  - Vogelezang, Suzanne
A1  - Vonk, Judith M.
A1  - Vrijkotte, Tanja G. M.
A1  - Vuoksimaa, Eero
A1  - Wang, Carol A.
A1  - Watkins, William J.
A1  - Wichmann, H-Erich
A1  - Willemsen, Gonneke
A1  - Williams, Gail M.
A1  - Wilson, James F.
A1  - Wray, Naomi R.
A1  - Xu, Shujing
A1  - Xu, Cheng-Jian
A1  - Yaghootkar, Hanieh
A1  - Yi, Lu
A1  - Zafarmand, Mohammad Hadi
A1  - Zeggini, Eleftheria
A1  - Zemel, Babette S.
A1  - Hinney, Anke
A1  - Lakka, Timo A.
A1  - Whitehouse, Andrew J. O.
A1  - Sunyer, Jordi
A1  - Widen, Elisabeth E.
A1  - Feenstra, Bjarke
A1  - Sebert, Sylvain
A1  - Jacobsson, Bo
A1  - Njolstad, Pal R.
A1  - Stoltenberg, Camilla
A1  - Smith, George Davey
A1  - Lawlor, Debbie A.
A1  - Paternoster, Lavinia
A1  - Timpson, Nicholas J.
A1  - Ong, Ken K.
A1  - Bisgaard, Hans
A1  - Bonnelykke, Klaus
A1  - Jaddoe, Vincent W. V.
A1  - Tiemeier, Henning
A1  - Jarvelin, Marjo-Riitta
A1  - Evans, David M.
A1  - Perry, John R. B.
A1  - Grant, Struan F. A.
A1  - Boomsma, Dorret I.
A1  - Freathy, Rachel M.
A1  - McCarthy, Mark I.
A1  - Felix, Janine F.
T1  - The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia
BT  - design, results and future prospects
JF  - European journal of epidemiology
N2  - The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
KW  - Genetics
KW  - Consortium
KW  - Childhood traits and disorders
KW  - Longitudinal
Y1  - 2019
U6  - https://doi.org/10.1007/s10654-019-00502-9
SN  - 0393-2990
SN  - 1573-7284
VL  - 34
IS  - 3
SP  - 279
EP  - 300
PB  - Springer
CY  - Dordrecht
ER  - 
TY  - JOUR
A1  - Li, Jian
A1  - Wang, Zi-Neng
A1  - Chen, You-Peng
A1  - Dong, Yun-Peng
A1  - Mao, Xiao-Min
A1  - Hocher, Berthold
T1  - Association of fetal but not maternal P-glycoprotein C3435T polymorphism with fetal growth and birth weight, a possible risk factor for cardiovascular diseases in later life
JF  - Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion
N2  - Background: The multidrug transporter P-glycoprotein (PGP) is expressed in the human placenta. In particular the C3435T ABCB1 polymorphism was associated with altered tissue expression of PGP in the human placenta. However, the potential functional impact of this polymorphism on the offspring is unknown so far.
 Methods: We analyzed the impact of the ABCB1/C3435T polymorphism on fetal growth in 262 mother/child pairs. Fetal growth was assessed by differential ultrasound examination of the fetal body prior to birth and by measuring birth weight.
 Results: The maternal ABCB1/C3435T polymorphism showed no trend for an association with birth weight or any ultrasound parameter describing late gestational fetal body shape. Genotyping the newborns, however, demonstrated that newborns carrying two copies of the T allele had a birth weight of 3176.39 g, whereas CT and CC newborns had a birth weight of 3345.04 g (p = 0.022). Adjusting for gestational age at delivery, child's gender, maternal BM1, maternal age and body weight at delivery confirmed this finding (p = 0.009). Considering gestational day of late ultrasound examination, gestational age at delivery, child's gender, maternal BMI, maternal age and maternal body weight at delivery, the fetal ABCB1/C3435T genotype revealed likewise a significant negative correlation with abdominal diameter and abdominal circumference (R-2 = 0.538, p = 0.010 and R-2 = 0.534, p = 0.005, respectively).
 Conclusions: Low birth weight may be a risk factor for cardiovascular diseases in later life. The fetal ABCB1/C3435T gene polymorphism may contribute to this risk. Since PGP controls transport of various biological agents, we suggest that PGP is involved in the transport of biological agents to the fetus that are important for normal fetal growth.
Y1  - 2012
U6  - https://doi.org/10.7754/Clin.Lab.2012.110920
SN  - 1433-6510
VL  - 58
IS  - 9-10
SP  - 1085
EP  - 1089
PB  - Clin Lab Publ., Verl. Klinisches Labor
CY  - Heidelberg
ER  - 
TY  - JOUR
A1  - Hocher, Berthold
A1  - Oberthür, Dominik
A1  - Slowinski, Torsten
A1  - Querfeld, Uwe
A1  - Schäfer, Franz
A1  - Doyon, Anke
A1  - Tepel, Martin
A1  - Roth, Heinz J.
A1  - Grön, Hans J.
A1  - Reichetzeder, Christoph
A1  - Betzel, Christian
A1  - Armbruster, Franz Paul
T1  - Modeling of Oxidized PTH (oxPTH) and Non-oxidized PTH (n-oxPTH) Receptor Binding and Relationship of Oxidized to Non-Oxidized PTH in Children with Chronic Renal Failure, Adult Patients on Hemodialysis and Kidney Transplant Recipients
JF  - Kidney & blood pressure research : official organ of the Gesellschaft für Nephrologie
N2  - Background: The biological properties of oxidized and non-oxidized PTH are substantially different. Oxidized PTH (oxPTH) loses its PTH receptor-stimulating properties, whereas non-oxidized PTH (n-oxPTH) is a full agonist of the receptor. This was described in more than 20 well published studies in the 1970(s) and 80(s). However, PTH oxidation has been ignored during the development of PTH assays for clinical use so far. Even the nowadays used third generation assay systems do not consider oxidation of PTH. We recently developed an assay to differentiate between oxPTH and n-oxPTH. In the current study we established normal values for this assay system. Furthermore, we compare the ratio of oxPTH to n-oxPTH in different population with chronic renal failure: 620 children with renal failure stage 2-4 of the 4C study, 342 adult patients on dialysis, and 602 kidney transplant recipients. In addition, we performed modeling of the interaction of either oxPTH or n-oxPTH with the PTH receptor using biophysical structure approaches. Results: The children had the highest mean as well as maximum n-oxPTH concentrations as compared to adult patients (both patients on dialysis as well as kidney transplant recipients). The relationship between oxPTH and n-oxPTH of individual patients varied substantially in all three populations with renal impairment. The analysis of n-oxPTH in 89 healthy control subjects revealed that n-oxPTH concentrations in patient with renal failure were higher as compared to healthy adult controls (2.25-fold in children with renal failure, 1.53-fold in adult patients on dialysis, and 1.56-fold in kidney transplant recipients, respectively). Computer assisted biophysical structure modeling demonstrated, however, minor sterical- and/or electrostatic changes in oxPTH and n-oxPTH. This indicated that PTH oxidation may induce refolding of PTH and hence alters PTH-PTH receptor interaction via oxidation induced three-dimensional structure alteration of PTH. Conclusion: A huge proportion of circulating PTH measured by current state-of-the-art assay systems is oxidized and thus not biologically active. The relationship between oxPTH and n-oxPTH of individual patients varied substantially. Non-oxidized PTH concentrations are 1.5 - 2.25 fold higher in patients with renal failure as compared to health controls. Measurements of n-oxPTH may reflect the hormone status more precise. The iPTH measures describes most likely oxidative stress in patients with renal failure rather than the PTH hormone status. This, however, needs to be demonstrated in further clinical studies.
KW  - n-oxPTH
KW  - Chronic Renal Failure
KW  - Kidney Transplantation
KW  - Hemodialysis
KW  - Oxidation
KW  - PTH
KW  - Chronic Renal Failure in Children
Y1  - 2013
U6  - https://doi.org/10.1159/000350149
SN  - 1420-4096
SN  - 1423-0143
VL  - 37
IS  - 4-5
SP  - 240
EP  - 251
PB  - Karger
CY  - Basel
ER  - 
TY  - JOUR
A1  - Hasan, Ahmed Abdallah Abdalrahman Mohamed
A1  - Hocher, Berthold
T1  - Role of soluble and membrane-bound dipeptidyl peptidase-4 in diabetic nephropathy
JF  - Journal of Molecular Endocrinology
N2  - Diabetic nephropathy is one of the most frequent, devastating and costly complications of diabetes. The available therapeutic approaches are limited. Dipeptidyl peptidase type 4 (DPP-4) inhibitors represent a new class of glucose-lowering drugs that might also have reno-protective properties. DPP-4 exists in two forms: a plasma membranebound form and a soluble form, and can exert many biological actions mainly through its peptidase activity and interaction with extracellular matrix components. The kidneys have the highest DPP-4 expression level in mammalians. DPP-4 expression and urinary activity are up-regulated in diabetic nephropathy, highlighting its role as a potential target to manage diabetic nephropathy. Preclinical animal studies and some clinical data suggest that DPP-4 inhibitors decrease the progression of diabetic nephropathy in a blood pressure-and glucose-independent manner. Many studies reported that these reno-protective effects could be due to increased half-life of DPP-4 substrates such as glucagon-like peptide-1 (GLP-1) and stromal derived factor-1 alpha (SDF-1a). However, the underlying mechanisms are far from being completely understood and clearly need further investigations.
KW  - DPP-4
KW  - diabetic nephropathy
KW  - DPP-4 inhibitors
KW  - GLP-1 and SDF-1a
Y1  - 2017
U6  - https://doi.org/10.1530/JME-17-0005
SN  - 0952-5041
SN  - 1479-6813
VL  - 59
SP  - R1
EP  - R10
PB  - Bioscientifica LTD
CY  - Bristol
ER  - 
TY  - JOUR
A1  - Feger, Martina
A1  - Fajol, Abul
A1  - Lebedeva, Aleksandra
A1  - Meissner, Adrian
A1  - Michael, Diana
A1  - Völkl, Jakob
A1  - Alesutan, Ioana
A1  - Schleicher, Erwin
A1  - Reichetzeder, Christoph
A1  - Hocher, Berthold
A1  - Qadri, Syed M.
A1  - Lang, Florian
T1  - Effect of Carbon Monoxide Donor CORM-2 on Vitamin D-3 Metabolism
JF  - Kidney & blood pressure research : official organ of the Gesellschaft für Nephrologie
N2  - Background/Aims: Carbon monoxide (CO) interferes with cytochrome-dependent cellular functions and acts as gaseous transmitter. CO is released from CO-releasing molecules (CORM) including tricarbonyl-dichlororuthenium (II) dimer (CORM-2), molecules considered for the treatment of several disorders including vascular dysfunction, inflammation, tissue ischemia and organ rejection. Cytochrome P450-sensitive function include formation of 1,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3) by renal 25-hydroxyvitamin D-3 1-alpha-hydroxylase (Cyp27b1). The enzyme is regulated by PTH, FGF23 and klotho. 1,25(OH)(2)D-3 regulates Ca2+ and phosphate transport as well as klotho expression. The present study explored, whether CORM-2 influences 1,25(OH)(2)D-3 formation and klotho expression. Methods: Mice were treated with intravenous CORM-2 (20 mg/kg body weight). Plasma 1,25(OH)(2)D-3 and FGF23 concentrations were determined by ELISA, phosphate, calcium and creatinine concentrations by colorimetric methods, transcript levels by quantitative RT-PCR and protein expression by western blotting. Fgf23 mRNA transcript levels were further determined in rat osteosarcoma UMR106 cells without or with prior treatment for 24 hours with 20 mu M CORM-2. Results: CORM-2 injection within 24 hours significantly increased FGF23 plasma levels and decreased 1,25(OH)(2)D-3 plasma levels, renal Cyp27b1 gene expression as well as renal klotho protein abundance and transcript levels. Moreover, treatment of UMR106 cells with CORM-2 significantly increased Fgf23 transcript levels. Conclusion: CO-releasing molecule CORM-2 enhances FGF23 expression and release and decreases klotho expression and 1,25(OH)(2)D-3 synthesis.
KW  - CORM-2
KW  - 1,25-Dihydroxyvitamin D-3
KW  - Klotho
KW  - FGF23
KW  - Phosphate
KW  - Calcium
Y1  - 2013
U6  - https://doi.org/10.1159/000355730
SN  - 1420-4096
SN  - 1423-0143
VL  - 37
IS  - 4-5
SP  - 496
EP  - 505
PB  - Karger
CY  - Basel
ER  - 
TY  - JOUR
A1  - Chen, Yao
A1  - Wang, Guang
A1  - Wang, Xiao-yu
A1  - Ma, Zheng-lai
A1  - Chen, You-peng
A1  - Chuai, Manli
A1  - von Websky, Karoline
A1  - Hocher, Berthold
A1  - Yang, Xuesong
T1  - Effects of high salt-exposure on the development of retina and lens in 5.5-Day Chick Embryo
JF  - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry and pharmacology
N2  - Background/Aims: Excess maternal salt intake during pregnancy may alter fetal development. However; our knowledge on how an increased salt intake during pregnancy influences fetal eye development is limited. In this study, we investigated the effects of high salt treatment on the developing eyes in chick embryos, especially focusing on the development of the retina and the lens. Methods: 5.5 day chick embryos were exposed to 280mosm/l (n=17), or 300mosm/l (n=16) NaCl. The treated embryos were then incubated for 96 hours before they were fixed with 4% paraformaldehyde for H&E staining, whole mount embryo immunostaining and TUNEL staining. BrdU and PH3 incorporation experiments were performed on the chick embryos after high salt treatment. RT-PCR analyses were conducted from chick retina tissues. Results: We demonstrated that high-salt treatment altered the size of eyes in chick embryos, induced malformation of the eyes and impaired the development of the lens and the retina. We found an impaired expression of Paired box 6 (PAX6) and neuronal cells in the developing retina as revealed by neurofilament immunofluorescent staining. There was a reduction in the number of BrdU-positive cells and PH3-positive cells in the retina, indicating an impaired cell proliferation with high salt treatment. High salt treatment also resulted in an increased number of TUNEL-positive cells in the retina, indicating a higher amount of cell death. RT-PCR data displayed that the expression of the pro-apoptotic molecule nerve growth factor (NGF) in chick retina was increased and CyclinD1 was reduced with high-salt treatment. The size of the lens was reduced and Pax6 expression in the lens was significantly inhibited. High salt treatment was detrimental to the migration of neural crest cells. Conclusion: Taken together; our study demonstrated that high salt exposure of 5.5 day chick embryos led to an impairment of retina and lens development, possibly through interfering with Pax6 expression.
KW  - Chick embryos
KW  - High osmolarity
KW  - Retina
KW  - Lens
KW  - Pax6
Y1  - 2014
U6  - https://doi.org/10.1159/000363044
SN  - 1015-8987
SN  - 1421-9778
VL  - 34
IS  - 3
SP  - 804
EP  - 817
PB  - Karger
CY  - Basel
ER  - 
TY  - JOUR
A1  - Bär, Ludmilla
A1  - Feger, Martina
A1  - Fajol, Abul
A1  - Klotz, Lars-Oliver
A1  - Zeng, Shufei
A1  - Lang, Florian
A1  - Hocher, Berthold
A1  - Föller, Michael
T1  - Insulin suppresses the production of fibroblast growth factor 23 (FGF23)
JF  - Proceedings of the National Academy of Sciences of the United States of America
N2  - Fibroblast growth factor 23 (FGF23) is produced by bone cells and regulates renal phosphate and vitamin D metabolism, as well as causing left ventricular hypertrophy. FGF23 deficiency results in rapid aging, whereas high plasma FGF23 levels are found in several disorders, including kidney or cardiovascular diseases. Regulators of FGF23 production include parathyroid hormone (PTH), calcitriol, dietary phosphate, and inflammation. We report that insulin and insulin-like growth factor 1 (IGF1) are negative regulators of FGF23 production. In UMR106 osteoblast-like cells, insulin and IGF1 down-regulated FGF23 production by inhibiting the transcription factor forkhead box protein O1 (FOXO1) through phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB)/Akt signaling. Insulin deficiency caused a surge in the serum FGF23 concentration in mice, which was reversed by administration of insulin. In women, a highly significant negative correlation between FGF23 plasma concentration and increase in plasma insulin level following an oral glucose load was found. Our results provide strong evidence that insulin/IGF1dependent PI3K/PKB/Akt/FOXO1 signaling is a powerful suppressor of FGF23 production in vitro as well as in mice and in humans.
KW  - PI3K
KW  - PKB/Akt
KW  - Klotho
KW  - phosphate
Y1  - 2018
U6  - https://doi.org/10.1073/pnas.1800160115
SN  - 0027-8424
VL  - 115
IS  - 22
SP  - 5804
EP  - 5809
PB  - National Acad. of Sciences
CY  - Washington
ER  - 
TY  - JOUR
A1  - Beaumont, Robin N.
A1  - Warrington, Nicole M.
A1  - Cavadino, Alana
A1  - Tyrrell, Jessica
A1  - Nodzenski, Michael
A1  - Horikoshi, Momoko
A1  - Geller, Frank
A1  - Myhre, Ronny
A1  - Richmond, Rebecca C.
A1  - Paternoster, Lavinia
A1  - Bradfield, Jonathan P.
A1  - Kreiner-Moller, Eskil
A1  - Huikari, Ville
A1  - Metrustry, Sarah
A1  - Lunetta, Kathryn L.
A1  - Painter, Jodie N.
A1  - Hottenga, Jouke-Jan
A1  - Allard, Catherine
A1  - Barton, Sheila J.
A1  - Espinosa, Ana
A1  - Marsh, Julie A.
A1  - Potter, Catherine
A1  - Zhang, Ge
A1  - Ang, Wei
A1  - Berry, Diane J.
A1  - Bouchard, Luigi
A1  - Das, Shikta
A1  - Hakonarson, Hakon
A1  - Heikkinen, Jani
A1  - Helgeland, Oyvind
A1  - Hocher, Berthold
A1  - Hofman, Albert
A1  - Inskip, Hazel M.
A1  - Jones, Samuel E.
A1  - Kogevinas, Manolis
A1  - Lind, Penelope A.
A1  - Marullo, Letizia
A1  - Medland, Sarah E.
A1  - Murray, Anna
A1  - Murray, Jeffrey C.
A1  - Njolstad, Pal R.
A1  - Nohr, Ellen A.
A1  - Reichetzeder, Christoph
A1  - Ring, Susan M.
A1  - Ruth, Katherine S.
A1  - Santa-Marina, Loreto
A1  - Scholtens, Denise M.
A1  - Sebert, Sylvain
A1  - Sengpiel, Verena
A1  - Tuke, Marcus A.
A1  - Vaudel, Marc
A1  - Weedon, Michael N.
A1  - Willemsen, Gonneke
A1  - Wood, Andrew R.
A1  - Yaghootkar, Hanieh
A1  - Muglia, Louis J.
A1  - Bartels, Meike
A1  - Relton, Caroline L.
A1  - Pennell, Craig E.
A1  - Chatzi, Leda
A1  - Estivill, Xavier
A1  - Holloway, John W.
A1  - Boomsma, Dorret I.
A1  - Montgomery, Grant W.
A1  - Murabito, Joanne M.
A1  - Spector, Tim D.
A1  - Power, Christine
A1  - Jarvelin, Marjo-Ritta
A1  - Bisgaard, Hans
A1  - Grant, Struan F. A.
A1  - Sorensen, Thorkild I. A.
A1  - Jaddoe, Vincent W.
A1  - Jacobsson, Bo
A1  - Melbye, Mads
A1  - McCarthy, Mark I.
A1  - Hattersley, Andrew T.
A1  - Hayes, M. Geoffrey
A1  - Frayling, Timothy M.
A1  - Hivert, Marie-France
A1  - Felix, Janine F.
A1  - Hypponen, Elina
A1  - Lowe, William L.
A1  - Evans, David M.
A1  - Lawlor, Debbie A.
A1  - Feenstra, Bjarke
A1  - Freathy, Rachel M.
T1  - Genome-wide association study of offspring birth weight in 86 577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics
JF  - Human molecular genetics
N2  - Genome-wide association studies of birth weight have focused on fetal genetics, whereas relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86 577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother-child pairs to quantify the separate maternal and fetal genetic effects. Maternal SNPs at 10 loci (MTNR1B, HMGA2, SH2B3, KCNAB1, L3MBTL3, GCK, EBF1, TCF7L2, ACTL9, CYP3A7) were associated with offspring birth weight at P< 5 x 10(-8). In SEM analyses, at least 7 of the 10 associations were consistent with effects of the maternal genotype acting via the intrauterine environment, rather than via effects of shared alleles with the fetus. Variants, or correlated proxies, at many of the loci had been previously associated with adult traits, including fasting glucose (MTNR1B, GCK and TCF7L2) and sex hormone levels (CYP3A7), and one (EBF1) with gestational duration. The identified associations indicate that genetic effects on maternal glucose, cytochrome P450 activity and gestational duration, and potentially on maternal blood pressure and immune function, are relevant for fetal growth. Further characterization of these associations in mechanistic and causal analyses will enhance understanding of the potentially modifiable maternal determinants of fetal growth, with the goal of reducing the morbidity and mortality associated with low and high birth weights.
Y1  - 2018
U6  - https://doi.org/10.1093/hmg/ddx429
SN  - 0964-6906
SN  - 1460-2083
VL  - 27
IS  - 4
SP  - 742
EP  - 756
PB  - Oxford Univ. Press
CY  - Oxford
ER  -