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Lookup NU author(s): Professor Mark Walker
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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 tvas 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 tries 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.
Author(s): Walker M; Cassell PG; Saker PJ; Huxtable SJ; Kousta E; Jackson AE; Hattersley AT; Frayling TM; Kopelman PG; Ramachandran A; Snehelatha C; Hitman GA; McCarthy MI
Publication type: Article
Publication status: Published
ISSN (print): 0012-186X
ISSN (electronic): 1432-0428
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