Association between tyrosine hydroxylase polymorphisms and left ventricular structure in young normotensive men

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.