TY - JOUR A1 - Huber, Matthias A1 - Lezius, Susanne A1 - Reibis, Rona Katharina A1 - Treszl, Andras A1 - Kujawinska, Dorota A1 - Jakob, Stefanie A1 - Wegscheider, Karl A1 - Völler, Heinz A1 - Kreutz, Reinhold T1 - A Single Nucleotide Polymorphism near the CYP17A1 Gene Is Associated with Left Ventricular Mass in Hypertensive Patients under Pharmacotherapy JF - International journal of molecular sciences N2 - 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/m(2.7) 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. KW - clinical study KW - genetics KW - heart KW - hypertension KW - cytochrome P450 17A1 (Cyp17A1) Y1 - 2015 U6 - https://doi.org/10.3390/ijms160817456 SN - 1422-0067 VL - 16 IS - 8 SP - 17456 EP - 17468 PB - MDPI CY - Basel ER - TY - GEN A1 - Huber, Matthias A1 - Lezius, Susanne A1 - Reibis, Rona Katharina A1 - Treszl, Andras A1 - Kujawinska, Dorota A1 - Jakob, Stefanie A1 - Wegscheider, Karl A1 - Völler, Heinz A1 - Kreutz, Reinhold T1 - A single nucleotide polymorphism near the CYP17A1 gene is associated with left ventricular mass in hypertensive patients under pharmacotherapy N2 - 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. T3 - Zweitveröffentlichungen der Universität Potsdam : Humanwissenschaftliche Reihe - 333 KW - clinical study KW - genetics KW - heart KW - hypertension KW - cytochrome P450 17A1 (Cyp17A1) Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-400074 ER - TY - JOUR A1 - Huber, Matthias A1 - Treszl, Andras A1 - Reibis, Rona Katharina A1 - Teichmann, Christopher A1 - Zergibel, Irina A1 - Bolbrinker, Juliane A1 - Scholze, Juergen A1 - Wegscheider, Karl A1 - Völler, Heinz A1 - Kreutz, Reinhold T1 - Genetics of melatonin receptor type 2 is associated with left ventricular function in hypertensive patients treated according to guidelines JF - European journal of internal medicine : official journal of the European Federation of Internal Medicine N2 - 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 +/- 9.4 years, 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: 2.4 mm Hg, 95% confidence interval (CI): 0.3 to 4.5 mm Hg, 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. KW - Clinical study KW - Genetics KW - Heart KW - Hypertension KW - Melatonin receptor type 2 Y1 - 2013 U6 - https://doi.org/10.1016/j.ejim.2013.03.015 SN - 0953-6205 VL - 24 IS - 7 SP - 650 EP - 655 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Reibis, Rona Katharina A1 - Huber, Matthias A1 - Karoff, Marthin A1 - Kamke, Wolfram A1 - Kreutz, Reinhold A1 - Wegscheider, Karl A1 - Völler, Heinz T1 - Target organ damage and control of cardiovascular risk factors in hypertensive patients Evidence from the multicenter ESTher registry JF - Herz : cardiovascular diseases N2 - This study investigated the incidence of hypertensive target organ damage (TOD), control of cardiovascular risk factors, and the short-term prognosis in hypertensive patients under contemporary guideline-oriented therapy. A total of 1,377 consecutive patients (mean age 58.2 +/- 9.9 years, 82.2 % male) with arterial hypertension were included in the ESTher (Endorganschaden, Therapie und Verlauf - target organ damage, therapy, and course) registry at 15 rehabilitation clinics within the framework of the National Genome Research Network. Cardiovascular risk factors, medication, comorbidities, and glomerular filtration rate (GFR) were assessed. Left ventricular hypertrophy (LVH), left ventricular mass (LVM), left ventricular mass index (LVMI), and left ventricular ejection fraction (LVEF) were determined by two-dimensional echocardiography. The mean follow-up was 513 +/- 159 days. Changes in continuous parameters were tested by the t test, changes in discrete characteristics are presented by means of transition tables and tested with the McNemar test. The mean LVEF was 59.3 +/- 9.9 %, both mean LVM (238.6 +/- 101.5 g) and LVMI (54.0 +/- 23.6 g/m(2.7)) were increased while relative wall thickness (RWT, 0.46 +/- 0.18) indicated the presence of concentric LVH. Of the patients, 10.2 % displayed renal dysfunction (estimated GFR < 60 ml/min/1.73 m(2)). The 1.5-year overall mortality was 1.2 %. Compared with discharge, at follow-up the proportion of patients with blood pressure (BP) values < 140/90 mmHg decreased from 68.7 % to 55.0 % (p < 0.001) and with low-density lipoprotein (LDL) values < 100 mg/dl from 62.6 % to 38.1 % (p < 0.001). At follow-up significantly more patients displayed a GFR value of < 60 ml/min/1.73 m(2) (10.2 % vs. 16.0 %, p < 0.001). A significant proportion of hypertensive rehabilitation participants displayed TOD including LVH and renal dysfunction. Even after stringent BP reduction, a considerable increase in nephropathy could be found after 18 months. KW - Arterial hypertension KW - Prospective study KW - Left ventricular hypertrophy KW - Glomerular filtration rate KW - Cardiac rehabilitation Y1 - 2015 U6 - https://doi.org/10.1007/s00059-014-4189-8 SN - 0340-9937 SN - 1615-6692 VL - 40 SP - 209 EP - 216 PB - Urban & Vogel CY - München ER -