TY  - JOUR
A1  - Algharably, Engi A. H.
A1  - Bolbrinker, Juliane
A1  - Lezius, Susanne
A1  - Reibis, Rona Katharina
A1  - Wegscheider, Karl
A1  - Völler, Heinz
A1  - Kreutz, Reinhold
T1  - Uromodulin associates with cardiorenal function in patients with hypertension and cardiovascular disease
JF  - Journal of hypertension
N2  - 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.
KW  - blood pressure
KW  - cardiovascular complications
KW  - chronic kidney disease
KW  - genetics
KW  - hypertension
KW  - kidney function
KW  - organ damage
KW  - Tamm-Horsfall protein
Y1  - 2017
U6  - https://doi.org/10.1097/HJH.0000000000001432
SN  - 0263-6352
SN  - 1473-5598
VL  - 35
SP  - 2053
EP  - 2058
PB  - Lippincott Williams & Wilkins
CY  - Philadelphia
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  -