caa a22 4500 475771761 CHVBK 20180406123619.0 cr unu---uuuuu 170329e20001101xx s 000 0 eng 10.1007/s001250051569 doi (NATIONALLICENCE)springer-10.1007/s001250051569 Evidence that single nucleotide polymorphism in the uncoupling protein 3 (UCP3) gene influences fat distribution in women of European and Asian origin [Elektronische Daten] [P. G. Cassell, P. J. Saker, S. J. Huxtable, E. Kousta, A. E. Jackson, A. T. Hattersley, T. M. Frayling, M. Walker, P. G. Kopelman, A. Ramachandran, C. Snehelatha, G. A. Hitman, M. I. McCarthy] Abstract : Aims/hypothesis. Uncoupling proteins are mitochondrial transmembrane carriers implicated in the regulation of energy balance. Dysfunction of UCP3 (the predominant uncoupling protein in skeletal muscle) might therefore be expected to reduce thermogenic capacity, alter energy homeostasis and influence predisposition to obesity and Type II (non-insulin-dependent) diabetes mellitus. A variant in the putative promoter region of UCP3 (-55 c→t) has recently been identified, and an association with obesity reported in French subjects. Our aim was to study the pathophysiological role of this variant in diabetes-related and obesity-related traits using two distinct ethnic populations. Methods. The -55 c→t variant was genotyped in 85 South Indian and 150 European parent-offspring trios ascertained through Type II diabetic probands and in 455 South Indian subjects initially recruited to an urban survey into the prevalence of diabetes. Results. In South Indian and European parent-offspring trios there was no preferential transmission of either allele at the -55 c→t polymorphism to diabetic offspring (South Indians, p = 0.60; Europeans, p = 0.15). When family members were analysed for intermediate traits, the t-allele was associated with increased waist-to-hip ratio but only in females (South Indian mothers p = 0.036, daughters p = 0.032: European mothers p = 0.037, daughters p = 0.14). These findings were replicated in South Indian females from the population-based survey (p = 0.039). Conclusion/interpretation. The consistent association between the t-allele at this locus and increased waist-to-hip ratio in women from three separate data sets indicates that variation at this polymorphism (or another locus with which it is in linkage disequilibrium) influences fat distribution but that this effect is restricted to females. [Diabetologia (2000) 43: 1558-1564] Springer-Verlag Berlin Heidelberg, 2000 Keywords Uncoupling protein-3 nationallicence Europeans nationallicence South Indians nationallicence family association nationallicence fat distribution nationallicence body mass index nationallicence Type II diabetes nationallicence Cassell P. G. Department of Diabetes and Metabolic Medicine, St Bartholomews and the Royal London School of Medicine and Dentistry, Queen Mary and Westfield College, London, UK, GB aut Saker P. J. Division of Medicine, Imperial College Genetics and Genomics Research Institute and MRC Clinical Sciences Centre, Imperial College School of Medicine, London, UK, GB aut Huxtable S. J. Division of Medicine, Imperial College Genetics and Genomics Research Institute and MRC Clinical Sciences Centre, Imperial College School of Medicine, London, UK, GB aut Kousta E. Division of Medicine, Imperial College Genetics and Genomics Research Institute and MRC Clinical Sciences Centre, Imperial College School of Medicine, London, UK, GB aut Jackson A. E. Department of Diabetes and Metabolic Medicine, St Bartholomews and the Royal London School of Medicine and Dentistry, Queen Mary and Westfield College, London, UK, GB aut Hattersley A. T. Department of Diabetes and Vascular Medicine, School of Postgraduate Medicine and Health Sciences, University of Exeter, Exeter, UK, GB aut Frayling T. M. Department of Diabetes and Vascular Medicine, School of Postgraduate Medicine and Health Sciences, University of Exeter, Exeter, UK, GB aut Walker M. Department of Medicine, School of Medicine, Newcastle-upon-Tyne, UK, GB aut Kopelman P. G. Department of Diabetes and Metabolic Medicine, St Bartholomews and the Royal London School of Medicine and Dentistry, Queen Mary and Westfield College, London, UK, GB aut Ramachandran A. Diabetes Research Centre, Chennai, India, IN aut Snehelatha C. Diabetes Research Centre, Chennai, India, IN aut Hitman G. A. Department of Diabetes and Metabolic Medicine, St Bartholomews and the Royal London School of Medicine and Dentistry, Queen Mary and Westfield College, London, UK, GB aut McCarthy M. I. Division of Medicine, Imperial College Genetics and Genomics Research Institute and MRC Clinical Sciences Centre, Imperial College School of Medicine, London, UK, GB aut https://doi.org/10.1007/s001250051569 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s001250051569 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Cassell P. G. Department of Diabetes and Metabolic Medicine, St Bartholomews and the Royal London School of Medicine and Dentistry, Queen Mary and Westfield College, London, UK, GB aut NATIONALLICENCE 700 1- Saker P. J. Division of Medicine, Imperial College Genetics and Genomics Research Institute and MRC Clinical Sciences Centre, Imperial College School of Medicine, London, UK, GB aut NATIONALLICENCE 700 1- Huxtable S. J. Division of Medicine, Imperial College Genetics and Genomics Research Institute and MRC Clinical Sciences Centre, Imperial College School of Medicine, London, UK, GB aut NATIONALLICENCE 700 1- Kousta E. Division of Medicine, Imperial College Genetics and Genomics Research Institute and MRC Clinical Sciences Centre, Imperial College School of Medicine, London, UK, GB aut NATIONALLICENCE 700 1- Jackson A. E. Department of Diabetes and Metabolic Medicine, St Bartholomews and the Royal London School of Medicine and Dentistry, Queen Mary and Westfield College, London, UK, GB aut NATIONALLICENCE 700 1- Hattersley A. T. Department of Diabetes and Vascular Medicine, School of Postgraduate Medicine and Health Sciences, University of Exeter, Exeter, UK, GB aut NATIONALLICENCE 700 1- Frayling T. M. Department of Diabetes and Vascular Medicine, School of Postgraduate Medicine and Health Sciences, University of Exeter, Exeter, UK, GB aut NATIONALLICENCE 700 1- Walker M. Department of Medicine, School of Medicine, Newcastle-upon-Tyne, UK, GB aut NATIONALLICENCE 700 1- Kopelman P. G. Department of Diabetes and Metabolic Medicine, St Bartholomews and the Royal London School of Medicine and Dentistry, Queen Mary and Westfield College, London, UK, GB aut NATIONALLICENCE 700 1- Ramachandran A. Diabetes Research Centre, Chennai, India, IN aut NATIONALLICENCE 700 1- Snehelatha C. Diabetes Research Centre, Chennai, India, IN aut NATIONALLICENCE 700 1- Hitman G. A. Department of Diabetes and Metabolic Medicine, St Bartholomews and the Royal London School of Medicine and Dentistry, Queen Mary and Westfield College, London, UK, GB aut NATIONALLICENCE 700 1- McCarthy M. I. Division of Medicine, Imperial College Genetics and Genomics Research Institute and MRC Clinical Sciences Centre, Imperial College School of Medicine, London, UK, GB aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer