Role of genetic variation in insulin-like growth factor 1 receptor on insulin resistance and arterial hypertension
Role of genetic variation in insulin-like growth factor 1 receptor on insulin resistance and arterial hypertension
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DOI：
10.1097/hjh.0b013e328337f6d5
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发表时间：
2010-06-01
影响因子：
4.9
通讯作者：
Pirola, Carlos J.
中科院分区：
文献类型：
--
作者：
Sookoian, Silvia;Fernandez Gianotti, Tomas;Pirola, Carlos J.
目的进行两个阶段的研究，探讨基因变异的胰岛素抵抗和动脉hypertension.Methods和结果的风险的作用变异的选择进行了第一阶段的硅分析的原始全基因组关联数据集的基因参与代谢综合征的组成部分，授予糖尿病遗传学倡议和威康信托病例对照Consortium。我们首先在两个数据集中应用基因优先化的计算算法后，确定具有关联截止值（P < 0.05）的单核苷酸多态性。在更有希望的变异中，选择IGF 1 R的6个单核苷酸多态性（rs 11247362、rs 10902606、rs 1317459、rs 11854132、rs 2684761和rs 2715416）在我们的人群中进行进一步评估。一项基于人群的研究共纳入了1094名年龄为34.4 ± 8.6岁的男性。rs 2684761基因型与胰岛素抵抗显著相关（作为离散性状，每个G等位基因的优势比为1.27，95%可信区间为1.03-1.56，P = 0.026;稳态模型评估-胰岛素抵抗作为连续性状，P = 0.01）。还观察到rs 2684761与动脉高血压的显著相关性。（每G等位基因的优势比为1.29，95%可信区间为1.02-1.64，P = 0.037）在调整年龄和稳态模型评估-胰岛素抵抗后。结论我们的研究首次表明IGF 1 R变异体在个体对代谢综合征相关表型的易感性中的假定作用，特别是胰岛素抵抗和动脉高血压的风险。J Hypertens 28：1194-1202（C）2010 Wolters Kluwer Health垂直杆Lippincott威廉姆斯& Wilkins。
Objective To perform a two-stage study to explore the role of gene variants in the risk of insulin resistance and arterial hypertension.Methods and results The selection of variants was performed by a first stage of in-silico analysis of the original genome-wide association data sets on genes involved in metabolic syndrome components, granted by the Diabetes Genetics Initiative and the Wellcome Trust Case-Control Consortium. We started by identifying single-nucleotide polymorphisms with a cutoff for association (P < 0.05) in both data sets after the application of a computational algorithm of gene prioritization. Among the more promising variants, six single-nucleotide polymorphisms in IGF1R (rs11247362, rs10902606, rs1317459, rs11854132, rs2684761, and rs2715416) were selected for further evaluation in our population. Altogether, 1094 men, aged 34.4 +/- 8.6 years, were included in a population-based study. Genotypes of rs2684761 showed significant association with insulin resistance (as a discrete trait, odds ratio per G allele 1.27, 95% confidence interval 1.03-1.56, P = 0.026; and homeostasis model assessment-insulin resistance as a continuous trait, P = 0.01). A significant association of rs2684761 with arterial hypertension was also observed (odds ratio per G allele 1.29, 95% confidence interval 1.02-1.64, P = 0.037) after adjusting for age and homeostasis model assessment-insulin resistance.Conclusion Our study suggests for the first time a putative role of IGF1R variants in individual susceptibility to metabolic syndrome-related phenotypes, in particular on the risk of having insulin resistance and arterial hypertension. J Hypertens 28: 1194-1202 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.