TY - JOUR A1 - Horikoshi, Momoko A1 - Yaghootkar, Hanieh A1 - Mook-Kanamori, Dennis O. A1 - Sovio, Ulla A1 - Taal, H. Rob A1 - Hennig, Branwen J. A1 - Bradfield, Jonathan P. A1 - St Pourcain, Beate A1 - Evans, David M. A1 - Charoen, Pimphen A1 - Kaakinen, Marika A1 - Cousminer, Diana L. A1 - Lehtimaki, Terho A1 - Kreiner-Moller, Eskil A1 - Warrington, Nicole M. A1 - Bustamante, Mariona A1 - Feenstra, Bjarke A1 - Berry, Diane J. A1 - Thiering, Elisabeth A1 - Pfab, Thiemo A1 - Barton, Sheila J. A1 - Shields, Beverley M. A1 - Kerkhof, Marjan A1 - van Leeuwen, Elisabeth M. A1 - Fulford, Anthony J. A1 - Kutalik, Zoltan A1 - Zhao, Jing Hua A1 - den Hoed, Marcel A1 - Mahajan, Anubha A1 - Lindi, Virpi A1 - Goh, Liang-Kee A1 - Hottenga, Jouke-Jan A1 - Wu, Ying A1 - Raitakari, Olli T. A1 - Harder, Marie N. A1 - Meirhaeghe, Aline A1 - Ntalla, Ioanna A1 - Salem, Rany M. A1 - Jameson, Karen A. A1 - Zhou, Kaixin A1 - Monies, Dorota M. A1 - Lagou, Vasiliki A1 - Kirin, Mirna A1 - Heikkinen, Jani A1 - Adair, Linda S. A1 - Alkuraya, Fowzan S. A1 - Al-Odaib, Ali A1 - Amouyel, Philippe A1 - Andersson, Ehm Astrid A1 - Bennett, Amanda J. A1 - Blakemore, Alexandra I. F. A1 - Buxton, Jessica L. A1 - Dallongeville, Jean A1 - Das, Shikta A1 - de Geus, Eco J. C. A1 - Estivill, Xavier A1 - Flexeder, Claudia A1 - Froguel, Philippe A1 - Geller, Frank A1 - Godfrey, Keith M. A1 - Gottrand, Frederic A1 - Groves, Christopher J. A1 - Hansen, Torben A1 - Hirschhorn, Joel N. A1 - Hofman, Albert A1 - Hollegaard, Mads V. A1 - Hougaard, David M. A1 - Hyppoenen, Elina A1 - Inskip, Hazel M. A1 - Isaacs, Aaron A1 - Jorgensen, Torben A1 - Kanaka-Gantenbein, Christina A1 - Kemp, John P. A1 - Kiess, Wieland A1 - Kilpelainen, Tuomas O. A1 - Klopp, Norman A1 - Knight, Bridget A. A1 - Kuzawa, Christopher W. A1 - McMahon, George A1 - Newnham, John P. A1 - Niinikoski, Harri A1 - Oostra, Ben A. A1 - Pedersen, Louise A1 - Postma, Dirkje S. A1 - Ring, Susan M. A1 - Rivadeneira, Fernando A1 - Robertson, Neil R. A1 - Sebert, Sylvain A1 - Simell, Olli A1 - Slowinski, Torsten A1 - Tiesler, Carla M. T. A1 - Toenjes, Anke A1 - Vaag, Allan A1 - Viikari, Jorma S. A1 - Vink, Jacqueline M. A1 - Vissing, Nadja Hawwa A1 - Wareham, Nicholas J. A1 - Willemsen, Gonneke A1 - Witte, Daniel R. A1 - Zhang, Haitao A1 - Zhao, Jianhua A1 - Wilson, James F. A1 - Stumvoll, Michael A1 - Prentice, Andrew M. A1 - Meyer, Brian F. A1 - Pearson, Ewan R. A1 - Boreham, Colin A. G. A1 - Cooper, Cyrus A1 - Gillman, Matthew W. A1 - Dedoussis, George V. A1 - Moreno, Luis A. A1 - Pedersen, Oluf A1 - Saarinen, Maiju A1 - Mohlke, Karen L. A1 - Boomsma, Dorret I. A1 - Saw, Seang-Mei A1 - Lakka, Timo A. A1 - Koerner, Antje A1 - Loos, Ruth J. F. A1 - Ong, Ken K. A1 - Vollenweider, Peter A1 - van Duijn, Cornelia M. A1 - Koppelman, Gerard H. A1 - Hattersley, Andrew T. A1 - Holloway, John W. A1 - Hocher, Berthold A1 - Heinrich, Joachim A1 - Power, Chris A1 - Melbye, Mads A1 - Guxens, Monica A1 - Pennell, Craig E. A1 - Bonnelykke, Klaus A1 - Bisgaard, Hans A1 - Eriksson, Johan G. A1 - Widen, Elisabeth A1 - Hakonarson, Hakon A1 - Uitterlinden, Andre G. A1 - Pouta, Anneli A1 - Lawlor, Debbie A. A1 - Smith, George Davey A1 - Frayling, Timothy M. A1 - McCarthy, Mark I. A1 - Grant, Struan F. A. A1 - Jaddoe, Vincent W. V. A1 - Jarvelin, Marjo-Riitta A1 - Timpson, Nicholas J. A1 - Prokopenko, Inga A1 - Freathy, Rachel M. T1 - New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism JF - Nature genetics N2 - Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood(1). Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits(2). In an expanded genome-wide association metaanalysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism. Y1 - 2013 U6 - https://doi.org/10.1038/ng.2477 SN - 1061-4036 VL - 45 IS - 1 SP - 76 EP - U115 PB - Nature Publ. Group CY - New York ER - TY - JOUR A1 - Espe, Katharina M. A1 - Raila, Jens A1 - Henze, Andrea A1 - Blouin, Katja A1 - Schneider, Andreas A1 - Schmiedeke, Daniel A1 - Krane, Vera A1 - Pilz, Stefan A1 - Schweigert, Florian J. A1 - Hocher, Berthold A1 - Wanner, Christoph A1 - Drechsler, Christiane T1 - Low plasma alpha-tocopherol concentrations and adverse clinical outcomes in diabetic hemodialysis patients JF - Clinical journal of the American Society of Nephrology N2 - Background and objectives Trials with the antioxidant vitamin E have failed to show benefit in the general population. Considering the different causes of death in ESRD, this study investigated the association between plasma concentrations of alpha-tocopherol and specific clinical outcomes in diabetic hemodialysis patients. Design, settings, participants, & measurements In 1046 diabetic hemodialysis patients (participants of the German Diabetes and Dialysis Study), alpha-tocopherol was measured in plasma by reversed-phase HPLC. By Cox regression analyses, hazard ratios were determined for prespecified end points according to baseline plasma alpha-tocopherol levels: sudden death (n=134), myocardial infarction (n=172), stroke (n=89), combined cardiovascular events (n=398), fatal infection (n=107), and all-cause mortality (n=508). Results Patients had a mean age of 66 8 years, and mean plasma alpha-tocopherol level was 22.8+/-9.6 mu mol/L. Levels of alpha-tocopherol were highly correlated to triglycerides (r=0.63, P<0.001). Patients in the lowest alpha-tocopherol quartile had (in unadjusted analyses) a 79% higher risk of stroke and a 31% higher risk of all-cause mortality compared with patients in the highest quartile. The associations were attenuated after adjustment for confounders (hazard ratio(stroke)=1.56, 95% confidence interval=0.75-3.25; hazard ratio(mortality)=1.22, 95% confidence interval=0.89-1.69, respectively). There was no association between alpha-tocopherol and myocardial infarction, sudden death, or infectious death. Conclusions Plasma alpha-tocopherol concentrations were not independently associated with cardiovascular outcomes, infectious deaths, or all-cause mortality in diabetic hemodialysis patients. The lack of association can partly be explained by a confounding influence of malnutrition, which should be considered in the planning of trials to reduce cardiovascular risk in dialysis patients. Y1 - 2013 U6 - https://doi.org/10.2215/CJN.04880511 SN - 1555-9041 VL - 8 IS - 3 SP - 452 EP - 458 PB - American Society of Nephrology CY - Washington ER - TY - JOUR A1 - Rund, Katharina M. A1 - Heylmann, Daniel A1 - Seiwert, Nina A1 - Wecklein, Sabine A1 - Oger, Camille A1 - Galano, Jean-Marie A1 - Durand, Thierry A1 - Chen, Rongjun A1 - Güler, Faikah A1 - Fahrer, Jörg A1 - Bornhorst, Julia A1 - Schebb, Nils Helge T1 - Formation of trans-epoxy fatty acids correlates with formation of isoprostanes and could serve as biomarker of oxidative stress JF - Prostaglandins & Other Lipid Mediators N2 - In mammals, epoxy-polyunsaturated fatty acids (epoxy-PUFA) are enzymatically formed from naturally occurring all-cis PUFA by cytochrome P450 monooxygenases leading to the generation of cis-epoxy-PUFA (mixture of R,S- and S,R-enantiomers). In addition, also non-enzymatic chemical peroxidation gives rise to epoxy-PUFA leading to both, cis- and trans-epoxy-PUFA (mixture of R,R- and S,S-enantiomers). Here, we investigated for the first time trans-epoxy-PUFA and the trans/cis-epoxy-PUFA ratio as potential new biomarker of lipid peroxidation. Their formation was analyzed in correlation with the formation of isoprostanes (IsoP), which are commonly used as biomarkers of oxidative stress. Five oxidative stress models were investigated including incubations of three human cell lines as well as the in vivo model Caenorhabditis elegans with tert-butyl hydroperoxide (t-BOOH) and analysis of murine kidney tissue after renal ischemia reperfusion injury (IRI). A comprehensive set of IsoP and epoxy-PUFA derived from biologically relevant PUFA (ARA, EPA and DHA) was simultaneously quantified by LC-ESI(-)-MS/MS. Following renal IRI only a moderate increase in the kidney levels of IsoP and no relevant change in the trans/cis-epoxy-PUFA ratio was observed. In all investigated cell lines (HCT-116, HepG2 and Caki-2) as well as C. elegans a dose dependent increase of both, IsoP and the trans/cis-epoxy-PUFA ratio in response to the applied t-BOOH was observed. The different cell lines showed a distinct time dependent pattern consistent for both classes of autoxidatively formed oxylipins. Clear and highly significant correlations of the trans/cisepoxy-PUFA ratios with the IsoP levels were found in all investigated cell lines and C. elegans. Based on this, we suggest the trans/cis-epoxy-PUFA ratio as potential new biomarker of oxidative stress, which warrants further investigation. KW - Isoprostane KW - Trans-epoxy-fatty acid KW - Oxidative stress KW - Biomarker KW - Oxylipin KW - Eicosanoid Y1 - 2019 U6 - https://doi.org/10.1016/j.prostaglandins.2019.04.004 SN - 1098-8823 SN - 2212-196X VL - 144 PB - Elsevier CY - New York ER -