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PROTECTIVE EFFECT IN HYPERTENSIVE HEART DISEASE OF THE 1742GG GENOTYPE OF THE HUMAN CARDIOTROPHIN-1 GENE: 6D.03

Introduction: Both clinical and experimental evidence indicates that cardiotrophin-1 (CT-1) is a cytokine that is critically involved in the development of left ventricular hypertrophy (LVH). We have investigated the effect of the 1742(C/G) polymorphism of human CT-1 gene (CTF1) on CT-1 levels and LVH in human essential hypertension. Materials and Methods: We genotyped 514 normotensive subjects and 386 hypertensive patients for 1742(C/G) polymorphism. Serum levels of CT-1 were assessed in 681subjects by ELISA. LVH was assessed in 297 subjects by bidimensional echocardiography. Results: The prevalence of the GG genotype was significantly reduced in the hypertensive group (8.4% in normotensive subjects, 4.9% in hypertensive patients, P = 0.046) and further reduced in patients with LVH (11.5% in normotensive subjects without LVH, 12.2% in hypertensives patients without LVH, 2.6% in hypertensive patients with LVH, P = 0.008). In addition, subjects of GG genotype presented lower serum levels of CT-1 (GG: 147.1 ± 10.5 fmol/mL, CC/CG: 187.1 ± 4.8 fmol/mL, P = 0.036) and lower left ventricular mass index (LVMI) (GG: 91 ± 6 g/m2, CC/CG: 119 ± 3 g/m2, P = 0.002) than CC/CG genotype subjects. Multivariate analyses showed that the 1742(C/G) polymorphism was a significant determinant of CT-1 levels and also of LVMI, after adjusting for confounding factors such as age, sex, systolic blood pressure and antihypertensive treatment. Conclusions: Our data indicate that the 1742(C/G) polymorphism of human CT-1 is a novel genetic marker in LVH, as it is associated with the LVMI in essential hypertension. The GG genotype may be protective against LVH and the levels of CT-1 may be one of the mechanisms underlying the effect of the polymorphism.