Objective: 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.
Methods: 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.
Results: 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/m2; CC/CG, 119 ± 3 g/m2; 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.
Conclusion: 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.
aDivision of Cardiovascular Sciences, Center for Applied Medical Research, Spain
bDepartment of Internal Medicine, Spain
cDepartment of Cardiology and Cardiovascular Surgery, Spain
dLaboratory of Biochemistry, University Clinic, University of Navarra, Navarra, Spain
eHypertension Clinic, Department of Internal Medicine, Hospital Clínico, University of Valencia, Valencia, Spain
*P.A.R. and M.U.M. contributed equally to the writing of this article.
Received 3 March, 2010
Revised 7 May, 2010
Accepted 28 June, 2010
Correspondence to Dr Guillermo Zalba or Dr Javier Díez, Division of Cardiovascular Sciences, Center for Applied Medical Research, Avda. Pío XII 55, 31008 Pamplona, Spain Tel: +34 948194700; fax: +34 948194716; e-mail: firstname.lastname@example.org; email@example.com