Variation in the UCP2 and UCP3 genes associates with abdominal obesity and serum lipids: the Finnish Diabetes Prevention Study.
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.
Salopuro
Titta
T
University of Kuopio, Department of Clinical Nutrition and Food and Health Research Center, Kuopio, Finland. titta.salopuro@uku.fi
Pulkkinen
Leena
L
Lindström
Jaana
J
Kolehmainen
Marjukka
M
Tolppanen
Anna-Maija
AM
Eriksson
Johan G
JG
Valle
Timo T
TT
Aunola
Sirkka
S
Ilanne-Parikka
Pirjo
P
Keinänen-Kiukaanniemi
Sirkka
S
Tuomilehto
Jaakko
J
Laakso
Markku
M
Uusitupa
Matti
M
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
D007473:Ion Channels; D008055:Lipids; D024101:Mitochondrial Proteins; C000604389:UCP2 protein, human; C000604392:UCP3 protein, human; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3