RESUMEN
BACKGROUND: Aldosterone plays an important role in development of left ventricular (LV) hypertrophy and myocardial fibrosis. We assessed the influence of the T-344C polymorphism of aldosterone synthase - the rate-limiting enzyme in aldosterone biosynthesis - on the structure of the left ventricle in young normotensive men. DESIGN AND METHODS: The population included 113 normotensive mid-European Caucasian men aged 18-40 years (mean 27 +/- 5 years). The genotype was assessed using polymerase chain reaction with subsequent cleavage with restriction enzyme HAEIII (restriction fragment length polymorphism method) and visualization with ethidium bromide. Plasma renin activity (PRA) and plasma aldosterone were measured. All subjects were examined by echocardiography and LV mass was assessed by using M-mode based ASE formula. RESULTS: The distribution of the genotypes was TT 23%:TC 55%:CC 22%. There were no differences in blood pressure among the groups. Men with the TT genotype had significantly higher levels of PRA (2.7 +/- 1.7 vs 1.8 +/- 1.0 vs 1.8 +/- 1.1 ng/ml/h, p < 0.01) and slightly higher plasma levels of aldosterone (113 +/- 64 vs 93 +/- 43 vs 87 +/- 39 pg/ml, p = 0,12). In the whole population, LV mass index (LVMI) did not differ significantly among the genotypes (92 +/- 16 vs 86 +/- 18 vs 84 +/- 16 g/m, p=0.20). In the population divided according to PRA, subjects with high renin had significantly higher LVMI in presence of the TT genotype (95 +/- 17 vs 84 +/- 16 vs 81 +/- 15 g/m, p < 0.05). CONCLUSIONS: In agreement with previous studies, we found that the TT genotype of T-344C polymorphism of aldosterone synthase gene was associated with significantly higher levels of PRA in normotensive men. In subjects with high PRA, the TT genotype was associated with higher values of the LVMI.
Asunto(s)
Citocromo P-450 CYP11B2/genética , Hipertrofia Ventricular Izquierda/enzimología , Hipertrofia Ventricular Izquierda/genética , Polimorfismo de Nucleótido Simple , Adolescente , Adulto , Aldosterona/sangre , Alelos , Secuencia de Bases , Presión Sanguínea , Estudios Transversales , ADN/genética , Humanos , Hipertrofia Ventricular Izquierda/fisiopatología , Masculino , Renina/sangreRESUMEN
Tyrosine hydroxylase (TH) is a rate-limiting enzyme for catecholamine biosynthesis. Increased sympathetic activity is associated with an increased left ventricular (LV) mass. However, the influence of TH gene polymorphisms on LV structure and function has yet to be investigated. Here, we analyse the association of Val-81-Met and tetranucleotide TCAT repeat TH polymorphisms with LV structure and function (assessed by echocardiography) in 108 normotensive men aged < or = 35 years (mean age: 25+/-4 years) with body mass index (BMI) < or = 30 kg/m2 (mean BMI: 23+/-3 kg/m2). The distribution of genotypes was VV homozygotes (n=42), VM heterozygotes (n=49) and MM homozygotes (n=17). The Val-81-Met polymorphism showed significant linkage disequilibrium with the TCAT polymorphism (P<0.0001). No differences were seen between the subgroups with respect to age, BMI and blood pressure. Compared with the VV and VM genotypes, subjects with the MM genotype showed significantly (all P<0.05) increased LV cavity diameter (VV: 52.8+/-3.9 mm, VM: 52.9+/-3.6 mm, MM: 56.1+/-3.2 mm), global LV mass (VV: 159+/-31 g, VM: 165+/-36 g, MM: 187+/-30 g) and LV mass index (VV: 81+/-14 g/m2, VM: 84+/-17 g/m2, MM: 93+/-12 g/m2). No differences were seen between the subgroups in parameters of LV function. In addition, plasma epinephrine and norepinephrine levels were comparable in the three subgroups. The results suggest an important association between the MM genotype of Val-81-Met TH gene polymorphism and increased LV cavity dimension and mass in a young normotensive male population, indicating an important role for genetic determination of the sympathetic system in LV growth.