Associations between polymorphisms in the mitochondrial uncoupling proteins (UCPs) with T2DM
Associations between polymorphisms in the mitochondrial uncoupling proteins (UCPs) with T2DM
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DOI：
10.1016/j.cca.2008.07.029
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发表时间：
2008-12-01
影响因子：
5
通讯作者：
Oh, Bermseok
中科院分区：
文献类型：
--
作者：
Lee, Hye-Ja;Ryu, Ha-Jung;Oh, Bermseok
背景：线粒体解偶联蛋白（UCPs）被认为是能量和葡萄糖稳态的关键调节因子。我们检测了UCP基因23个单核苷酸多态性（single nucleotide polymorphisms，SNPs）对2型糖尿病（type 2 diabetes mellitus，T2 DM）及其相关表型的影响，以确定可能参与T2 DM易感性的遗传因素。以及24个个体的UCP基因的内含子-外显子边界。对761例2型糖尿病患者和632例非糖尿病对照者的23个单核苷酸多态性进行基因分型，并分析其与2型糖尿病的相关性。结果：UCP 2 - 5331 G>A（P=0.018，OR =1.38）与2型糖尿病的相关性。95%CI（置信区间）=1.06-1.79），UCP 2 - 3998 C>G（P=0.021，OR=1.37，95%CI =1.05-1.78），UCP 2 + 320 C>T（P=0.019，OR=0.73，95%CI =0.57-0.95）。3个SNP之间存在较强的连锁不平衡（LD）（r（2）=0.94-0.97）。UCP 2 - 5331 G>A是一个调节性SNP（rSNP），在肥胖或腹型肥胖受试者中与T2 DM显著相关（P=0.017，OR=1.78，95%CI =1.11-2.85; P=0.004）。OR=1.82。95%CI =1.21-2.74;分别）。UCP 3 - 2078 C>T的SNP仅在女性中与T2 DM相关（P=0.026，OR=0.71）。95%CI =0.52-0.96）。具有rSNPs UCP 2 - 5331 G>A和UCP 3 - 2078 C>T组合的患者显示出T2 DM的风险增加。具体来说易感等位基因中两个rSNP纯合子的患者比一个rSNP杂合子和另一个rSNP纯合子的患者患2型糖尿病的风险更高（P=0.033，OR=1.38）。95% CI-1.03-1.85）。这种关联在女性中更为明显（P=0.022，OR=1.58）。结论：UCP 2 - 5331 G>A和UCP 3 - 2078 C>T多态性是韩国人T2 DM的易感性标志。(C)2008 Elsevier B. V.保留所有权利。
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.