Associations between polymorphisms in the mitochondrial uncoupling proteins (UCPs) with T2DM

초록

Background: Mitochondrial uncoupling proteins (UCPs) are considered pivotal regulators of energy and glucose homeostasis. We examined the effect of 23 single nucleotide polymorphisms (SNPs) in the UCP genes on type 2 diabetes mellitus (T2DM) and related phenotypes to identify genetic factors that may be involved in susceptibility to T2DM. Methods: We directly sequenced the coding region, portions of the 5'- and 3'-flanking sequences. and the intron-exon boundaries of the UCP genes from 24 individuals. We genotyped 23 SNPs in 761 unrelated patients with T2DM and 632 unrelated non-diabetic control subjects and investigated their potential involvement in T2DM. Results: We identified association between T2DM and the following 3 SNPs in UCP2: UCP2 -5331G>A (P=0.018, odds ratio(OR)=1.38. 95% CI (confidence interval)=1.06-1.79), UCP2 -3998C>G (P=0.021, OR=1.37, 95% CI=1.05-1.78), and UCP2 +320C>T (P=0.019, OR=0.73, 95% CI=0.57-0.95). There was strong linkage disequilibrium (LD) among these 3 SNPs (r(2)=0.94-0.97). UCP2 -5331G>A is a regulatory SNP (rSNP), and its association with T2DM was significant among obese or abdominally obese subjects (P=0.017, OR=1.78, 95% CI=1.11-2.85; P=0.004. OR=1.82. 95% CI=1.21-2.74; respectively). UCP3 -2078C>T of UCP3 SNPs was associated with T2DM only among women (P=0.026, OR=0.71. 95% CI=0.52-0.96). Patients with combinations of the rSNPs UCP2 -5331G>A and UCP3 -2078C>T displayed an increased risk for T2DM. Specifically. those patients homozygous for both rSNPs among susceptible alleles had a higher risk for T2DM than patients heterozygous for one rSNP and homozygous for the other rSNP (P=0.033, OR=1.38. 95% CI-1.03-1.85). This association was more obvious in women (P=0.022, OR=1.58. 95% CI=1.07-2.34). Conclusions: Our results suggest that the UCP2 -5331G>A and UCP3 -2078C>T polymorphisms are susceptibility markers for T2DM among Koreans. (C) 2008 Elsevier B.V. All rights reserved.

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