The private hepatocyte nuclear factor-1α G319S variant is associated with plasma lipoprotein variation in Canadian Oji-Cree
The private hepatocyte nuclear factor-1α G319S variant is associated with plasma lipoprotein variation in Canadian Oji-Cree
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DOI：
10.1161/01.atv.20.1.217
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发表时间：
2000-01-01
影响因子：
8.7
通讯作者：
Connelly, PW
中科院分区：
文献类型：
--
作者：
Hegele, RA;Cao, HN;Connelly, PW
我们之前表明，2 型糖尿病与肝细胞核转录因子 (HNF)-1 α 中的一种私有多态性（即 G319S）之间存在极强的关联。由于 HNF-1 α 参与多个载脂蛋白基因的转录，因此我们在 55 名患有 2 型糖尿病的无关 Oji-Cree 受试者和 175 名不患有 2 型糖尿病的无关 Oji-Cree 受试者的样本中测试了私有 HNF1A G319S 变体与血浆脂蛋白之间的关联。在患有 2 型糖尿病的 Oji-Cree 受试者中，我们发现 HNF1A G319S 基因型与较低的血浆总胆固醇、低密度脂蛋白胆固醇和载脂蛋白 (apo) B 浓度显着相关。在没有 2 型糖尿病的 Oji-Cree 受试者中，我们发现 HNF1A G319S 基因型与较高的血浆浓度显着相关。 高密度脂蛋白胆固醇和载脂蛋白AI的血浆浓度。与血浆甘油三酯或脂蛋白(a) 没有关联。回归分析表明，HNF1A 基因型约占糖尿病受试者中 apo B 相关性状变异的 10%，约占非糖尿病受试者中 apo AI 相关性状变异的 5%。此外，回归模型表明，HNF1A S319 等位基因在患有和不患有 2 型糖尿病的受试者中以显性方式影响这些特征。这些发现提供了第一个证据，证明核转录因子中的罕见变异与血浆脂蛋白性状的变异有关。
We previously showed an extremely strong association between type 2 diabetes and a private polymorphism, namely G319S, in the hepatocyte nuclear transcription factor (HNF)-1 alpha. Because HNF-1 alpha is involved in the transcription of several apolipoprotein genes, we tested for an association between the private HNF1A G319S variant and plasma lipoproteins in a sample of 55 unrelated Oji-Cree subjects with type 2 diabetes and 175 unrelated Oji-Cree subjects without type 2 diabetes. in Oji-Cree subjects with type 2 diabetes, we found that the HNF1A G319S genotype was significantly associated with lower plasma concentrations of total cholesterol, low density lipoprotein cholesterol, and apolipoprotein (apo) B, In Oji-Cree subjects without type 2 diabetes, we found that the HNF1A G319S genotype was significantly associated with higher plasma concentrations of high density lipoprotein cholesterol and apo AI. There were no associations with plasma triglycerides or lipoprotein(a). Regression analysis indicated that the HNF1A genotype accounted for approximate to 10% of the variation in the apo B-related traits in the diabetic subjects and for approximate to 5% of the variation in the apo AI-related traits in the nondiabetic subjects. Furthermore, the regression model indicated that the HNF1A S319 allele affected these traits in a dominant manner in subjects with and without type 2 diabetes. These findings provide the first evidence that a rare variant in a nuclear transcription factor is associated with variation in plasma lipoprotein traits.