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.