Association of insulin-like growth factor-1 receptor gene polymorphisms with left ventricular mass and geometry in essential hypertension

Abstract

Stimulation of insulin-like growth factor (IGF)-1 receptor by IGF-1 and insulin strongly induces cardiomyocyte hypertrophy. In this study, we assessed the hypothesis that genetic variations of the IGF-1 receptor may be linked to the diversity of left ventricular (LV) structure in hypertensive patients. Genotypes in 12 single nucleotide polymorphisms (SNPs) of the IGF-1 receptor gene identified by direct sequencing were determined in 795 Japanese patients with essential hypertension. In echocardiographic examinations, LV mass index (LVMI) and relative wall thickness (RWT) were measured. Among 12 SNPs, promoter -328C>T and intron-13 275124A>C polymorphisms were significantly associated with LV hypertrophy (LVMI> or =125 g m(-2)) and concentric change (RWT> or =0.44), respectively. In allele frequencies, the C allele of -328C>T was related to LV hypertrophy, and the A allele of 275124A>C was related to LV concentric change. In fact, LVMI and prevalence of LV hypertrophy increased in CC genotype of -328C>T. RWT and prevalence of LV concentric change increased in AA genotype of 275124A>C. A multiple logistic regression analysis revealed that the presence of CC genotype of -328C>T or AA genotype of 275124A>C was an independent determinant for LV hypertrophy or concentric change, respectively. Furthermore, the combination of CC of -328C>T and AA of 275124A>C genotypes was significantly associated with abnormal LV geometry, especially concentric hypertrophy. Our findings show that two SNPs of the IGF-1 receptor gene are related to LV hypertrophy in patients with essential hypertension, suggesting that the genetic variation of the IGF-1 receptor may be involved in the diversity of LV structure in hypertensives.