The frequent UCP2 -866G>A polymorphism protects against insulin resistance and is associated with obesity: a study of obesity and related metabolic traits among 17¿636 Danes
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The frequent UCP2 -866G>A polymorphism protects against insulin resistance and is associated with obesity : a study of obesity and related metabolic traits among 17¿636 Danes. / Andersen, G; Dalgaard, L T; Justesen, J M; Anthonsen, S; Nielsen, T; Thørner, L W; Witte, D; Jørgensen, T; Clausen, J O; Lauritzen, Torsten; Holmkvist, J; Hansen, T; Pedersen, O.
I: International Journal of Obesity, 2012.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - The frequent UCP2 -866G>A polymorphism protects against insulin resistance and is associated with obesity
T2 - a study of obesity and related metabolic traits among 17¿636 Danes
AU - Andersen, G
AU - Dalgaard, L T
AU - Justesen, J M
AU - Anthonsen, S
AU - Nielsen, T
AU - Thørner, L W
AU - Witte, D
AU - Jørgensen, T
AU - Clausen, J O
AU - Lauritzen, Torsten
AU - Holmkvist, J
AU - Hansen, T
AU - Pedersen, O
PY - 2012
Y1 - 2012
N2 - CONTEXT:Uncoupling protein 2 (UCP2) is involved in regulating ATP synthesis, generation of reactive oxygen species and glucose-stimulated insulin secretion in ß-cells. Polymorphisms in UCP2 may be associated with obesity and type 2 diabetes mellitus.OBJECTIVE:To determine the influence of a functional UCP2 promoter polymorphism (-866G>A, rs659366) on obesity, type 2 diabetes and intermediary metabolic traits. Furthermore, to include these and previously published data in a meta-analysis of this variant with respect to its impact on obesity and type 2 diabetes.DESIGN:We genotyped UCP2 rs659366 in a total of 17¿636 Danish individuals and established case-control studies of obese and non-obese subjects and of type 2 diabetic and glucose-tolerant subjects. Meta-analyses were made in own data set and in publicly available data sets. Quantitative traits relevant for obesity and type 2 diabetes were analysed within separate study populations.RESULTS:We found no consistent associations between the UCP2 -866G-allele and obesity or type 2 diabetes. Yet, a meta-analysis of data from 12¿984 subjects showed an association with obesity (GA vs GG odds ratio (OR) (95% confidence interval (CI)): 0.894(0.826-0.968) P=0.00562, and AA vs GG OR(95% CI): 0.892(0.800-0.996), P=0.0415. Moreover, a meta-analysis for type 2 diabetes of 15¿107 individuals showed no association. The -866G-allele was associated with elevated fasting serum insulin levels (P=0.002) and HOMA insulin resistance index (P=0.0007). Insulin sensitivity measured during intravenous glucose tolerance test in young Caucasian subjects (n=377) was decreased in carriers of the GG genotype (P=0.05).CONCLUSIONS:The UCP2 -866G-allele is associated with decreased insulin sensitivity in Danish subjects and is associated with obesity in a combined meta-analysis.International Journal of Obesity advance online publication, 21 February 2012; doi:10.1038/ijo.2012.22.
AB - CONTEXT:Uncoupling protein 2 (UCP2) is involved in regulating ATP synthesis, generation of reactive oxygen species and glucose-stimulated insulin secretion in ß-cells. Polymorphisms in UCP2 may be associated with obesity and type 2 diabetes mellitus.OBJECTIVE:To determine the influence of a functional UCP2 promoter polymorphism (-866G>A, rs659366) on obesity, type 2 diabetes and intermediary metabolic traits. Furthermore, to include these and previously published data in a meta-analysis of this variant with respect to its impact on obesity and type 2 diabetes.DESIGN:We genotyped UCP2 rs659366 in a total of 17¿636 Danish individuals and established case-control studies of obese and non-obese subjects and of type 2 diabetic and glucose-tolerant subjects. Meta-analyses were made in own data set and in publicly available data sets. Quantitative traits relevant for obesity and type 2 diabetes were analysed within separate study populations.RESULTS:We found no consistent associations between the UCP2 -866G-allele and obesity or type 2 diabetes. Yet, a meta-analysis of data from 12¿984 subjects showed an association with obesity (GA vs GG odds ratio (OR) (95% confidence interval (CI)): 0.894(0.826-0.968) P=0.00562, and AA vs GG OR(95% CI): 0.892(0.800-0.996), P=0.0415. Moreover, a meta-analysis for type 2 diabetes of 15¿107 individuals showed no association. The -866G-allele was associated with elevated fasting serum insulin levels (P=0.002) and HOMA insulin resistance index (P=0.0007). Insulin sensitivity measured during intravenous glucose tolerance test in young Caucasian subjects (n=377) was decreased in carriers of the GG genotype (P=0.05).CONCLUSIONS:The UCP2 -866G-allele is associated with decreased insulin sensitivity in Danish subjects and is associated with obesity in a combined meta-analysis.International Journal of Obesity advance online publication, 21 February 2012; doi:10.1038/ijo.2012.22.
U2 - 10.1038/ijo.2012.22
DO - 10.1038/ijo.2012.22
M3 - Journal article
C2 - 22349573
JO - International Journal of Obesity
JF - International Journal of Obesity
SN - 0307-0565
ER -
ID: 40309783