title: Variation in the UCP2 and UCP3 genes associates with abdominal obesity and serum lipids: the Finnish Diabetes Prevention Study.
abstract: 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/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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Kuopio, Department of Clinical Nutrition and Food and Health Research Center, Kuopio, Finland. titta.salopuro@uku.fi
authors.forename: Titta
authors.initials: T
authors.lastname: Salopuro
authors.forename: Leena
authors.initials: L
authors.lastname: Pulkkinen
authors.forename: Jaana
authors.initials: J
authors.lastname: Lindström
authors.forename: Marjukka
authors.initials: M
authors.lastname: Kolehmainen
authors.forename: Anna-Maija
authors.initials: AM
authors.lastname: Tolppanen
authors.forename: Johan G
authors.initials: JG
authors.lastname: Eriksson
authors.forename: Timo T
authors.initials: TT
authors.lastname: Valle
authors.forename: Sirkka
authors.initials: S
authors.lastname: Aunola
authors.forename: Pirjo
authors.initials: P
authors.lastname: Ilanne-Parikka
authors.forename: Sirkka
authors.initials: S
authors.lastname: Keinänen-Kiukaanniemi
authors.forename: Jaakko
authors.initials: J
authors.lastname: Tuomilehto
authors.forename: Markku
authors.initials: M
authors.lastname: Laakso
authors.forename: Matti
authors.initials: M
authors.lastname: Uusitupa
mesh_terms: D000328:Adult; D005260:Female; D005387:Finland; D005500:Follow-Up Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007473:Ion Channels / Q000235:genetics*; D015810:Linkage Disequilibrium; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics*; D009765:Obesity / Q000097:blood / Q000235:genetics* / Q000628:therapy; D020641:Polymorphism, Single Nucleotide; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3; D049629:Waist-Hip Ratio
chemical_list: D007473:Ion Channels; D008055:Lipids; D024101:Mitochondrial Proteins; C000604389:UCP2 protein, human; C000604392:UCP3 protein, human; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3