Insulin-Like Growth Factor-1 and Receptor Contribute Genetic Susceptibility to Hypertension in a Han Chinese Population

Abstract

Insulin-like growth factor 1 (IGF-1) and IGF-1 receptor (IGF-1R) have been suggested to mediate the pathophysiological response to elevated blood pressure. This study aims to evaluate the association of IGF-1 and IGF-1R with hypertension. METHODS Overall, 2,012 hypertensive cases and 2,210 controls were included in a case-control study, and 10 tagging single nucleotide polymorphisms (tagSNPs) were selected. The association of these SNPs with hypertension was further evaluated in a follow-up analysis and in an adolescent population. RESULTS A case-control study indicated that rs1815009 and rs2654981 in IGF-1R were significantly associated with hypertension, with odds ratios of 0.89 (P = 0.009) and 1.19 (P = 0.034), respectively, after adjusting for covariates. Stratification analyses revealed significant associations with hypertension (P < 0.05) for rs35767 in normal weight and obese populations; for rs2229765 in individuals <55 years of age and in overweight and nondrinking populations; and for rs2002880 in overweight and drinking populations. In a follow-up study, rs13379905 in IGF-1R was associated with hypertension incidence (hazard ratio, HR = 1.24, P = 0.042). This association was more significant in individuals with a hypertensive family history (HR = 2.10, P = 0.001). The association of rs13379905 with prehypertension and hypertension was further replicated in adolescent males (P = 0.005). Significant associations with hypertension incidence (P < 0.05) were observed for rs6219 in individuals <55 years of age and among those with obesity and a hypertensive family history as well as rs2002880 in obese individuals. CONCLUSIONS Our findings suggest that IGF-1R may contribute to the genetic susceptibility to hypertension, with BMI, age, and family history of hypertension all potentially modulating the genetic effects of IGF-1 on hypertension.