Impact of common type 2 diabetes risk Polymorphisms in the DESIR prospective study
Impact of common type 2 diabetes risk Polymorphisms in the DESIR prospective study
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DOI：
10.2337/db07-0615
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发表时间：
2008-01-01
期刊：
影响因子：
7.7
通讯作者：
Froguel, Philippe
中科院分区：
文献类型：
--
作者：
Vaxillaire, Martine;Veslot, Jacques;Froguel, Philippe
目的：2型糖尿病遗传学的新图景涉及不同组合的基因变异，每种变异都随着环境暴露适度增加风险。然而，这些基因与疾病预测的相关性尚未得到广泛测试。研究设计和方法-我们分析了14个已知候选基因的19个常见多态性，以了解它们对DESIR（来自胰岛素抵抗综合征流行病学研究的数据）前瞻性研究中葡萄糖耐受不良的患病率和发病率的贡献，包括3877名参与者（9年研究后，16.8%患有高血糖症，7.9%患有糖尿病）。结果：随访研究结束时，GCK（葡萄糖激酶）- 30A等位基因与2型糖尿病风险增加相关(在一个加性模型下，校正OR为1.34 [95% CI 1.07-1.691]，独立的法国糖尿病病例受试者（OR为1.22,P = 0.007），空腹血糖升高（每个A等位基因0.85%,P = 6 × 10(-5)），体内平衡模型评估P细胞功能降低（40%,P = 0.0009）。il -6（白细胞介素-6）-174 G/C在疾病风险中与年龄相互作用，并根据年龄调节空腹血糖（56岁降低1.36%,P = 5 × 10(-5)）。这些多态性与KCNJ11 (Kir6.2)-E23K和TCF7L2-rs7903146可能预测DESIR队列中的糖尿病发病率。与无风险等位基因或无风险等位基因的携带者相比，GCK、TCF7L2和IL6每增加一个风险等位基因，风险增加1.34 (P = 2 × 10(-6))， OR为2.48 （95% CI 1.59-3.86）。结论：我们的数据证实了一般人群中2型糖尿病的几种高危多态性，并表明前瞻性研究是补充经典遗传方法的有价值的设计。
OBJECTIVE-The emerging picture of type 2 diabetes genetics involves differently assembled gene variants, each modestly increasing risk with environmental exposure. However, the relevance of these genes for disease prediction has not been extensively tested.RESEARCH DESIGN AND METHODS-We analyzed 19 common polymorphisms of 14 known candidate genes for their contribution to prevalence and incidence of glucose intolerance in the DESIR (Data from an Epidemiological Study on the Insulin Resistance syndrome) prospective study of middle-aged Caucasian subjects, including 3,877 participants (16.8% with hyperglycemia and 7.9% with diabetes after the 9-year study).RESULTS-The GCK (Glucokinase) - 30A allele was associated with increased type 2 diabetes risk at the end of the follow-up study (adjusted OR 1.34 [95% CI 1.07-1.691) under an additive model, as supported in independent French diabetic case subjects (OR 1.22, P = 0.007), with increased fasting glycemia (0.85% per A allele, P = 6 x 10(-5)) and decreased homeostasis model assessment of P-cell function (40%, P = 0.0009). IL6 (Interleukin-6) -174 G/C interacts with age in disease risk and modulates fasting glycemia according to age (1.36% decrease over 56 years, P = 5 x 10(-5)). These polymorphisms together with KCNJ11 (Kir6.2)-E23K and TCF7L2-rs7903146 may predict diabetes incidence in the DESIR cohort. Each additional risk allele at GCK, TCF7L2, and IL6 increased risk by 1.34 (P = 2 x 10(-6)), with an OR of 2.48 (95% CI 1.59-3.86), in carriers of at least four at-risk alleles compared with those with none or one risk allele.CONCLUSIONS-Our data confirm several at-risk polymorphisms for type 2 diabetes in a general population and demonstrate that prospective studies are valuable designs to complement classical genetic approaches.