A Single Nucleotide Polymorphism near the CYP17A1 Gene Is Associated with Left Ventricular Mass in Hypertensive Patients under Pharmacotherapy.

Cytochrome P450 17A1 (CYP17A1) catalyses the formation and metabolism of steroid hormones. They are involved in blood pressure (BP) regulation and in the pathogenesis of left ventricular hypertrophy. Therefore, altered function of CYP17A1 due to genetic variants may influence BP and left ventricular mass. Notably, genome wide association studies supported the role of this enzyme in BP control. Against this background, we investigated associations between single nucleotide polymorphisms (SNPs) in or nearby the CYP17A1 gene with BP and left ventricular mass in patients with arterial hypertension and associated cardiovascular organ damage treated according to guidelines. Patients (n = 1007, mean age 58.0 ± 9.8 years, 83% men) with arterial hypertension and cardiac left ventricular ejection fraction (LVEF) ≥ 40% were enrolled in the study. Cardiac parameters of left ventricular mass, geometry and function were determined by echocardiography. The cohort comprised patients with coronary heart disease (n = 823; 81.7%) and myocardial infarction (n = 545; 54.1%) with a mean LVEF of 59.9% ± 9.3%. The mean left ventricular mass index (LVMI) was 52.1 ± 21.2 g/m2.7 and 485 (48.2%) patients had left ventricular hypertrophy. There was no significant association of any investigated SNP (rs619824, rs743572, rs1004467, rs11191548, rs17115100) with mean 24 h systolic or diastolic BP. However, carriers of the rs11191548 C allele demonstrated a 7% increase in LVMI (95% CI: 1%-12%, p = 0.017) compared to non-carriers. The CYP17A1 polymorphism rs11191548 demonstrated a significant association with LVMI in patients with arterial hypertension and preserved LVEF. Thus, CYP17A1 may contribute to cardiac hypertrophy in this clinical condition.

Role of the angiotensin II type 2 receptor gene (+1675G/A) polymorphism on left ventricular hypertrophy and geometry in treated hypertensive patients.

OBJECTIVE: A genetic polymorphism in the angiotensin II type 2 receptor (AGTR2 +1675G/A) has been associated with left ventricular hypertrophy (LVH). We tested whether this polymorphism affects LVH and left ventricular geometry parameters in patients with essential hypertension and cardiovascular disease who are treated according to guidelines. METHODS: We analyzed a cohort of 208 women and 1030 men with essential hypertension, associated cardiovascular disease and left ventricular ejection fractions 40% or more. Previous cardiac diseases included coronary heart disease (81%) and myocardial infarction (MI; 52%). Ten parameters of left ventricular mass, geometry and function were determined by echocardiography. Genotyping was performed by PCR. Due to the X chromosomal location of AGTR2, genotype-phenotype analysis was separated for women and men. Statistical analysis was performed by univariate and multivariate analysis accounting for confounding factors. RESULTS: The mean age was 58.4 +/- 10 years. In the overall cohort, mean left ventricular mass index was 54 +/- 23.6 g/h without significant differences between patients with and without MI. The frequency of LVH (49% overall) was also similar in patients with or without MI. In men, AGTR2 +1675G/A had no influence on echocardiographic parameters. Similar findings were obtained in women, with the exception that the thickness of the interventricular septum was significantly lower in A allele carriers (-11%) in both crude (P = 0.002) and multivariate analysis (P = 0.044). CONCLUSION: In treated patients with arterial hypertension, cardiac disease and preserved left ventricular systolic function AGTR2 (+1675G/A) exhibits only a minor effect on left ventricular geometry in women and none in men.