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


CONCLUSIONS
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.
Robador
Pablo A
PA
Division of Cardiovascular Sciences, Center for Applied Medical Research, Spain.
Moreno
María U
MU
Beloqui
Oscar
O
Varo
Nerea
N
Redón
Josep
J
Fortuño
Ana
A
Zalba
Guillermo
G
Díez
Javier
J
D000483:Alleles; D001794:Blood Pressure; D016207:Cytokines / Q000235:genetics*; D004452:Echocardiography / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000235:genetics*; D017379:Hypertrophy, Left Ventricular / Q000150:complications / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic
D016207:Cytokines; C092073:cardiotrophin 1