@article{AlgharablyBolbrinkerLeziusetal.2017,
  author    = {Algharably, Engi A. H. and Bolbrinker, Juliane and Lezius, Susanne and Reibis, Rona Katharina and Wegscheider, Karl and V{\"o}ller, Heinz and Kreutz, Reinhold},
  title     = {Uromodulin associates with cardiorenal function in patients with hypertension and cardiovascular disease},
  series = {Journal of hypertension},
  volume    = {35},
  journal   = {Journal of hypertension},
  publisher = {Lippincott Williams \& Wilkins},
  address   = {Philadelphia},
  issn      = {0263-6352},
  doi       = {10.1097/HJH.0000000000001432},
  pages     = {2053 -- 2058},
  year      = {2017},
  abstract  = {Objective:Common genetic variants in the gene encoding uromodulin (UMOD) have been associated with renal function, blood pressure (BP) and hypertension. We investigated the associations between an important single nucleotide polymorphism (SNP) in UMOD, that is rs12917707-G>T, and estimated glomerular filtration rate (eGFR), BP and cardiac organ damage as determined by echocardiography in patients with arterial hypertension.Methods:A cohort of 1218 treated high-risk patients (mean age 58.5 years, 83\% men) with documented cardiovascular disease (81\% with coronary heart disease) was analysed.Results:The mean values for 24-h SBP and DBP were 124.714.7 and 73.9 +/- 9.4mmHg; mean eGFR was 77.5 +/- 18.3ml/min per 1.73m(2), mean left ventricular ejection fraction was 59.3 +/- 9.9\% and mean left ventricular mass index in men and women was 53.9 +/- 23.2 and 54.9 +/- 23.7g/m(2.7) with 50.4\% of patients having left ventricular hypertrophy. A significant association between rs12917707 and eGFR was observed with T-allele carriers showing significantly higher eGFR values (+2.6ml/min per 1.73m(2), P=0.006) than noncarriers. This SNP associated also with left atrial diameter (P=0.007); homozygous carriers of the T-allele had smaller left atrial diameter (-1.5mm) than other genotype groups (P=0.040). No significant associations between rs12917707 and other cardiac or BP phenotypes were observed.Conclusions:These findings extend the previously documented role of UMOD for renal function also to treated high-risk patients with arterial hypertension and reveal a novel association with left atrial remodelling and thus a potential cardiorenal link modulated by UMOD.},
  language  = {en}
}
@article{HuberTreszlReibisetal.2013,
  author    = {Huber, Matthias and Treszl, Andras and Reibis, Rona Katharina and Teichmann, Christopher and Zergibel, Irina and Bolbrinker, Juliane and Scholze, Juergen and Wegscheider, Karl and V{\"o}ller, Heinz and Kreutz, Reinhold},
  title     = {Genetics of melatonin receptor type 2 is associated with left ventricular function in hypertensive patients treated according to guidelines},
  series = {European journal of internal medicine : official journal of the European Federation of Internal Medicine},
  volume    = {24},
  journal   = {European journal of internal medicine : official journal of the European Federation of Internal Medicine},
  number    = {7},
  publisher = {Elsevier},
  address   = {Amsterdam},
  issn      = {0953-6205},
  doi       = {10.1016/j.ejim.2013.03.015},
  pages     = {650 -- 655},
  year      = {2013},
  abstract  = {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.},
  language  = {en}
}
@article{HuberLeziusReibisetal.2015,
  author    = {Huber, Matthias and Lezius, Susanne and Reibis, Rona Katharina and Treszl, Andras and Kujawinska, Dorota and Jakob, Stefanie and Wegscheider, Karl and V{\"o}ller, Heinz and Kreutz, Reinhold},
  title     = {A Single Nucleotide Polymorphism near the CYP17A1 Gene Is Associated with Left Ventricular Mass in Hypertensive Patients under Pharmacotherapy},
  series = {International journal of molecular sciences},
  volume    = {16},
  journal   = {International journal of molecular sciences},
  number    = {8},
  publisher = {MDPI},
  address   = {Basel},
  issn      = {1422-0067},
  doi       = {10.3390/ijms160817456},
  pages     = {17456 -- 17468},
  year      = {2015},
  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/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.},
  language  = {en}
}
@article{ReibisHuberKaroffetal.2015,
  author    = {Reibis, Rona Katharina and Huber, Matthias and Karoff, Marthin and Kamke, Wolfram and Kreutz, Reinhold and Wegscheider, Karl and V{\"o}ller, Heinz},
  title     = {Target organ damage and control of cardiovascular risk factors in hypertensive patients Evidence from the multicenter ESTher registry},
  series = {Herz : cardiovascular diseases},
  volume    = {40},
  journal   = {Herz : cardiovascular diseases},
  publisher = {Urban \& Vogel},
  address   = {M{\"u}nchen},
  issn      = {0340-9937},
  doi       = {10.1007/s00059-014-4189-8},
  pages     = {209 -- 216},
  year      = {2015},
  abstract  = {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.},
  language  = {en}
}