Polymorphisms of the peroxisome proliferator-activated receptor-γ coactivator-1α gene are associated with hypertrophic cardiomyopathy and not with hypertension hypertrophy

Background: The clinical phenotype of both hypertrophic cardiomyopathy (HCM) and left ventricular hypertrophy (LVH) induced by hypertension is heterogeneous. Genetic factors may contribute to this heterogeneity. Evidence is accumulating that the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) gene plays a role in cardiac hypertrophy. The aim of our study was to identify the association between PGC-1α gene polymorphisms and cardiac hypertrophy. Methods: A total of 270 consecutive HCM patients and 2486 hypertensive patients, comprising 1180 with LVH and 1306 without LVH, as well as 894 healthy controls, were successfully investigated. Polymorphisms of the PGC-1α gene were genotyped by PCR-restriction fragment length polymorphism and confirmed by sequencing. Results: The Ser482 allele (rs8192678 G>A and A>A) and CC genotype of Thr394Thr (rs2970847) conferred increased risk for HCM [odds ratio (OR) 1.52, 95% confidence interval (Cl) 1.11-2.11; OR 1.49, 95% Cl 1.15-1.98, respectively]. The maximum ventricular thickness was greater in HCM patients carrying the Ser482 risk allele than in carriers of the non-risk allele (20.7±4.1 vs. 19.1±4.3 mm, p<0.05) and for the CC Thr394Thr genotype (20.9±4.6 vs. 19.0±4.2 mm, p<0.05). No association was found between PGC-1α polymorphism and hypertension with or without LVH. Conclusions: Our data indicate that variants of the PGC-1α gene are correlated with increased risk for HCM.