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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. [ABSTRACT FROM AUTHOR]

Background: Melatonin exerts multiple biological effects with potential impact on human diseases. This is underscored by genetic studies that demonstrated associations between melatonin receptor type 2 gene (MTNR1B) polymorphisms and characteristics of type 2 diabetes. We set out to test the hypothesis whether genetic variants at MTNR1B are also relevant for other disease phenotypes within the cardiovascular continuum. We thus investigated single nucleotide polymorphisms (SNPs) of MTNR1B in relation to blood pressure (BP) and cardiac parameters in hypertensive patients. Methods: Patients (n=605, mean age 56.2±9.4years, 82.3% male) with arterial hypertension and cardiac ejection fraction (EF) ≥40% were studied. Cardiac parameters were assessed by echocardiography. Results: The cohort comprised subjects with coronary heart disease (73.1%) and myocardial infarction (48.1%) with a mean EF of 63.7±8.9%. Analysis of SNPs rs10830962, rs4753426, rs12804291, rs10830963, and rs3781638 revealed two haplotypes 1 and 2 with frequencies of 0.402 and 0.277, respectively. Carriers with haplotype 1 (CTCCC) showed compared to non-carriers a higher mean 24-hour systolic BP (difference BP: 2.4mmHg, 95% confidence interval (CI): 0.3 to 4.5mmHg, p=0.023). Haplotype 2 (GCCGA) was significantly related to EF with an absolute increase of 1.8% (CI: 0.45 to 3.14%) in carriers versus non-carriers (p=0.009). Conclusion: Genetics of MTNR1B point to impact of the melatonin signalling pathway for BP and left ventricular function. This may support the importance of the melatonin system as a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Telomere length has emerged as a biological correlate for ageing, which in turn is a risk factor for the manifestation of cardiovascular diseases. This study investigated the relation between leucocyte telomere length (LTL) and its genetic background to cardiac structure and function in patients with arterial hypertension. We analysed a cohort of 1,106 treated hypertensive patients (83.3% males; mean age, 57.9 ± 9.8 years) with an ejection fraction (EF) over 40% and documented cardiovascular disease or target organ damage. LTL and genotypes of single nucleotide polymorphisms (SNPs), previously implicated in LTL, were determined by real-time PCR. The mean left ventricular mass index (LVMI) and EF were 51.8 ± 21.0 g/H and 61.1 ± 9.6%, respectively. In multivariate adjusted analysis, a 1.5-fold LTL was positively related with a 2.2% increase of LVMI (CI = 0.1% to 4.2%, p = 0.044) and an absolute increase in EF of 0.6% (CI = 0.1% to 1.1%, p = 0.028). One SNP near TERC (rs16847897) showed a significant absolute difference in EF dependent on allele status (rs16847897, G allele 2.7%; CI = 0.7% to 4.6%; p = 0.008, p = 0.048, after adjustment for multiple testing). This applied also for two SNPs in BICD1 (rs2630578, C allele −1.8%; CI = −2.8% to −0.7%; p = 0.002, p = 0.018; rs1151026, G allele −1.9%, CI = −3.0% to −0.8%; p < 0.001, p = 0.002) with the extension that a frequent haplotype in BICD1 showed an absolute −1.8% (CI = −3.0% to −0.7%; p = 0.002, p = 0.008) lower EF compared with those lacking this haplotype. Our results point to a role of genetic variants recently implicated in LTL for left ventricular function in hypertensive patients. [ABSTRACT FROM AUTHOR]