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

Abstract

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.

Common Polymorphisms at the CYP17A1 Locus Associate With Steroid Phenotype

“…6-9 A recent study has also associated rs11191548 with left ventricular mass index (LVMI) in hypertensive patients, which is suggestive of a role in cardiac hypertrophy. 10 Rare genetic variants at CYP17A1 are already known to cause hypertension and so this locus represents a rare concurrence of blood pressure candidate gene studies with GWAS evidence.…”

Association of CYP17A1 Genetic Polymorphisms and Susceptibility to Essential Hypertension in the Southwest Han Chinese Population

“…An associated study among European ancestry participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium indicated that polymorphism rs743572 was associated with BP traits [ 39 ]. Another recent study conducted in patients with arterial hypertension and cardiac left ventricular ejection fraction revealed that no significant association was found between SNP rs743572 and mean 24-h systolic or diastolic BP [ 40 ]. In our study, no association was observed between this polymorphism and EH among the Han Chinese population.…”

Brief Overview of a Decade of Genome-Wide Association Studies on Primary Hypertension

“…CYP17A1 encodes 17 α -hydroxylase which is essential to the synthesis of cortisol precursors. Therefore, alteration of this gene can cause a deficiency in 17 α -hydroxylase and thus cortisol, which affects blood pressure [ 57 ]. Supporting the role of CYP17A1 in blood pressure regulation is the SNP rs11191548, a SNP near the CYP17A1 gene that has been consistently associated with blood pressure in both East Asian cohorts and Caucasian cohorts [ 10 , 17 , 18 , 58 – 60 ].…”