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Mitochondrial uncoupling protein gene cluster variation (UCP2-UCP3) and the risk of incident type 2 diabetes mellitus: the Women's Genome Health Study.

ABSTRACT: Uncoupling protein 2, mitochondrial, (UCP2) gene variation has recently been implicated in type 2 diabetes mellitus (T2DM). To date, no prospective epidemiological data are available.The association between 14 UCP (UCP2-UCP3) gene cluster tagging-SNPs and incident T2DM was investigated in 22,715 Caucasian participants of the prospective Women's Genome Health Study. All were free of known cardiovascular disease and diabetes at baseline. During a 13-year follow-up period, 1445 participants developed an incident T2DM. Multivariable Cox regression analysis was performed to investigate the relationship between genotypes and T2DM risk assuming an additive model. Stratified analysis by smoking status, and haplotype analysis were also performed.No evidence for an association of any of the tagging-SNPs tested with T2DM risk. Further investigation using stratified analysis, and haplotype-based approach showed similar null findings.The present investigation suggests that the UCP gene cluster variation may not be useful predictor for T2DM risk assessment.

SUBMITTER: Zee RY

PROVIDER: S-EPMC3018667 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Mitochondrial uncoupling protein gene cluster variation (UCP2-UCP3) and the risk of incident type 2 diabetes mellitus: the Women's Genome Health Study.

Zee Robert Y L RY Ridker Paul M PM Chasman Daniel I DI

Atherosclerosis 20101020 1

<h4>Objective</h4>Uncoupling protein 2, mitochondrial, (UCP2) gene variation has recently been implicated in type 2 diabetes mellitus (T2DM). To date, no prospective epidemiological data are available.<h4>Methods</h4>The association between 14 UCP (UCP2-UCP3) gene cluster tagging-SNPs and incident T2DM was investigated in 22,715 Caucasian participants of the prospective Women's Genome Health Study. All were free of known cardiovascular disease and diabetes at baseline. During a 13-year follow-up ...[more]

PMID: 21074158

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Project description:We explored the associations of three variants in the uncoupling protein 2 (UCP2) gene, one variant in the UCP2-UCP3 intergenic region and five variants in the uncoupling protein 3 (UCP3) gene with obesity and diabetes related traits in subjects with impaired glucose tolerance participating in Finnish Diabetes Prevention Study. Altogether 507 overweight individuals (body mass index: 31.2 +/- 4.5 kg/m2, age: 55 +/- 7 years) for whom DNA was available were randomized to either an intensified diet and physical activity group or to a conventional care control group.We analysed the data from the baseline and annual follow-up visits from years 1, 2 and 3. Measurements of anthropometry, plasma glucose and serum insulin in oral glucose tolerance test, serum total cholesterol, HDL-cholesterol and triglycerides were included. The median follow-up time for type 2 diabetes incidence was 7 years. Genetic variants were screened by restriction fragment length polymorphism or Illumina method.UCP3 gene variant rs3781907 was associated with increased serum total and LDL-cholesterol levels, at baseline and during the follow-up period. The same variant was associated with a higher risk of type 2 diabetes. Variants rs1726745, rs11235972 and rs1800849 in the UCP3 gene associated with serum total and LDL-cholesterol at baseline. Haploblock including variants rs659366, rs653529, rs15763, and rs1726745 was associated with measures of abdominal obesity at baseline and in the longitudinal analysis. The haplotype comprising alleles rs659366-G, rs653529-A, rs15763-G and rs1726745-A was associated with higher waist-to-hip ratio, and haplotype comprising alleles rs3781907-G, rs11235972-A, and rs1800849-T was associated with increased serum total and LDL-cholesterol concentrations.Genetic variation in the UCP2-UCP3 gene cluster may act as a modifier increasing serum lipid levels and indices of abdominal obesity, and may thereby also contribute to the metabolic aberrations observed in obesity and type 2 diabetes.

Dataset Information

Mitochondrial uncoupling protein gene cluster variation (UCP2-UCP3) and the risk of incident type 2 diabetes mellitus: the Women's Genome Health Study.

Publications

Mitochondrial uncoupling protein gene cluster variation (UCP2-UCP3) and the risk of incident type 2 diabetes mellitus: the Women's Genome Health Study.

Similar Datasets

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