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载脂蛋白 E-219G/T 和+113G/C 多态性影响土耳其人群的胰岛素抵抗。

The APOE -219G/T and +113G/C polymorphisms affect insulin resistance among Turks.

机构信息

Department of Genetics, Institute for Experimental Medicine, Istanbul University, 34080, Istanbul, Turkey.

出版信息

Metabolism. 2011 May;60(5):655-63. doi: 10.1016/j.metabol.2010.06.016. Epub 2010 Aug 17.

Abstract

The -219G/T (rs405509) and +113G/C (rs440446) polymorphisms within the regulatory region of the apolipoprotein E (APOE) gene have been related to the transcriptional activity of the gene. We examined the effect of the stated polymorphisms and their construct haplotypes with the APOE ɛ2/ɛ3/ɛ4 polymorphism on lipid levels and insulin resistance in the Turkish Adult Risk Factor Study. Randomly selected 1774 adults (mean age, 55.0 ± 11.7 years; 51.2% women) participating in the population-based Turkish Adult Risk Factor Study were cross-sectionally analyzed for the -219G/T, +113G/C, and ɛ2/ɛ3/ɛ4 polymorphisms as well as their haplotypes. Insulin resistance was defined as the 70th percentile in the sample (>2.51) of the homeostatic model assessment (HOMA). The frequencies of the -219T and +113C alleles were 0.477 and 0.423, respectively; and those of haplotype 1 (GGɛ3) and haplotype 2 (TCɛ3) were 44.1% and 41.9%, respectively. The -219G/T and +113G/C genotypes (both P < .04) and diplotypes of haplotype 2 (TCɛ3) (P < .014) were inversely related to serum fasting insulin and the HOMA index, even after controlling for 8 relevant covariates, but not to serum lipids. Within the APOE3 group, haplotype 2 (TC-/TC+) heterozygotes had an odds ratio of 0.66 (95% confidence interval, 0.42-0.99) for HOMA of insulin resistance after adjusting for 8 covariates. APOE promoter polymorphisms and their diplotypes are independently related with serum fasting insulin levels and HOMA index among Turks.

摘要

载脂蛋白 E(APOE)基因调控区的-219G/T(rs405509)和+113G/C(rs440446)多态性与基因的转录活性有关。我们研究了所述多态性及其与 APOE ε2/ε3/ε4 多态性构建的单体型对土耳其成人危险因素研究中血脂水平和胰岛素抵抗的影响。我们对 1774 名随机选择的成年人(平均年龄 55.0±11.7 岁,51.2%为女性)进行了横断面分析,以检测-219G/T、+113G/C 和 ε2/ε3/ε4 多态性及其单体型。胰岛素抵抗的定义为样品中稳态模型评估(HOMA)的第 70 百分位数(>2.51)。-219T 和 +113C 等位基因的频率分别为 0.477 和 0.423;单体型 1(GGε3)和单体型 2(TCε3)的频率分别为 44.1%和 41.9%。-219G/T 和 +113G/C 基因型(均 P<0.04)和单体型 2(TCε3)的二倍型(P<0.014)与血清空腹胰岛素和 HOMA 指数呈负相关,即使在控制了 8 个相关协变量后也是如此,但与血清脂质无关。在 APOE3 组中,调整了 8 个协变量后,单体型 2(TC-/TC+)杂合子的胰岛素抵抗 HOMA 的比值比为 0.66(95%置信区间,0.42-0.99)。在土耳其人中,APOE 启动子多态性及其二倍型与血清空腹胰岛素水平和 HOMA 指数独立相关。

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