Role of genetic variation in insulin-like growth factor 1 receptor on insulin resistance and arterial hypertension.

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.