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Background  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/m 2 , 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.    Methods  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.    Results   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.    Conclusion  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.

Variation in the UCP2 and UCP3genes associates with abdominal obesity and serum lipids: The Finnish Diabetes Prevention Study