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Genetic variation in UCP2 (uncoupling protein-2) is associated with energy metabolism in Pima Indians.

Abstract：

AIMS/HYPOTHESIS:Uncoupling protein-2 (UCP2) is thought to play a role in insulin secretion and the development of obesity. In this study, we investigated the effects of genetic variation in UCP2 on type 2 diabetes and obesity, as well as on metabolic phenotypes related to these diseases, in Pima Indians. METHODS:The coding and untranslated regions of UCP2, and approximately 1 kb of the 5' upstream region, were sequenced in DNA samples taken from 83 extremely obese Pima Indians who were not first-degree relatives. RESULTS:Five variants were identified: (1) a -866G/A in the 5' upstream region; (2) a G/A in exon 2; (3) a C/T resulting in an Ala55Val substitution in exon 4; and (4, 5) two insertion/deletions (ins/del; 45-bp and 3-bp) in the 3' untranslated region. Among the 83 subjects whose DNA was sequenced, the -866G/A was in complete genotypic concordance with the Ala55Val and the 3-bp ins/del polymorphism. The G/A polymorphism in exon 2 was extremely rare. To capture the common variation in this gene for association analyses, the -866G/A variant (as a representative of Ala55Val and the 3-bp ins/del polymorphism) and the 45-bp ins/del were also genotyped for 864 full-blooded Pima Indians. Neither of these variants was associated with type 2 diabetes or body mass index. However, in a subgroup of 185 subjects who had undergone detailed metabolic measurements, these variants were associated with 24-h energy expenditure as measured in a human metabolic chamber (p=0.007 for the 45-bp ins/del and p=0.03 for the -866G/A after adjusting for age, sex, family membership, fat-free mass and fat mass). CONCLUSIONS/INTERPRETATION:Our data indicate that variation in UCP2 may play a role in energy metabolism, but this gene does not contribute significantly to the aetiology of type 2 diabetes and/or obesity in Pima Indians.

journal_name

Diabetologia

journal_title

Diabetologia

authors

Kovacs P,Ma L,Hanson RL,Franks P,Stumvoll M,Bogardus C,Baier LJ

doi

10.1007/s00125-005-1934-9

subject

Has Abstract

pub_date

2005-11-01 00:00:00

pages

2292-5

issue

11

eissn

0012-186X

issn

1432-0428

journal_volume

48

pub_type

杂志文章

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