Protective effect of the 1742(C/G) polymorphism of human cardiotrophin-1 against left ventricular hypertrophy in essential hypertension

Abstract

Experimental and clinical evidence supports a role of cardiotrophin-1 (CT-1) in the development of hypertensive left ventricular hypertrophy (LVH). The goal of this study was to investigate the relationship between human CT-1 genetic background and LVH in essential hypertension. A total of 900 individuals were genotyped for the 1742(C/G) polymorphism of the human CT-1 gene. Serum CT-1 levels were assessed by ELISA in 681 individuals. Left ventricular parameters were determined by two-dimensional echocardiography in 297 individuals. The prevalence of the GG genotype of the 1742(C/G) polymorphism was reduced in essential hypertension (8.4% in normotensive individuals, 4.9% in hypertensive patients, P = 0.046 versus CC/CG individuals) and in LVH (11.5% in nonhypertrophic normotensive individuals, 12.2% in nonhypertrophic hypertensive patients, 2.6% in hypertensive patients with LVH, P = 0.008 versus CC/CG individuals). Apart from this, GG individuals presented lower serum concentration of CT-1 (GG, 147.1 ± 10.5 fmol/ml; CC/CG, 187.1 ± 4.8 fmol/ml; P = 0.036) and left ventricular mass index (GG, 91 ± 6 g/m; CC/CG, 119 ± 3 g/m; P = 0.002). Multivariate analyses showed that the 1742(C/G) polymorphism was a significant determinant of both left ventricular mass index and serum CT-1, after adjusting for confounding factors. Finally, in-vitro studies supported the functionality of the 1742(C/G) polymorphism. Our results indicate that the 1742(C/G) polymorphism of the human CT-1 gene is associated with LVH in hypertension and that the GG genotype may have a protective role. It is suggested that CT-1 is one of the mediators of this association.