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  - Tepel, Martin
A1  - Armbruster, Franz Paul
A1  - Groen, Hans Juergen
A1  - Scholze, Alexandra
A1  - Reichetzeder, Christoph
A1  - Roth, Heinz Jürgen
A1  - Hocher, Berthold
T1  - Nonoxidized, biologically active parathyroid hormone determines mortality in hemodialysis patients
JF  - The journal of clinical endocrinology & metabolism
N2  - Background: It was shown that nonoxidized PTH (n-oxPTH) is bioactive, whereas the oxidation of PTH results in a loss of biological activity.
 Methods: In this study we analyzed the association of n-oxPTH on mortality in hemodialysis patients using a recently developed assay system.
 Results: Hemodialysis patients (224 men, 116 women) had a median age of 66 years. One hundred seventy patients (50%) died during the follow-up period of 5 years. Median n-oxPTH levels were higher in survivors (7.2 ng/L) compared with deceased patients (5.0 ng/L; P = .002). Survival analysis showed an increased survival in the highest n-oxPTH tertile compared with the lowest n-oxPTH tertile (chi(2), 14.3; P = 0008). Median survival was 1702 days in the highest n-oxPTH tertile, whereas it was only 453 days in the lowest n-oxPTH tertile. Multivariable-adjusted Cox regression showed that higher age increased odds for death, whereas higher n-oxPTH reduced the odds for death. Another model analyzing a subgroup of patients with intact PTH (iPTH) concentrations at baseline above the upper normal range of the iPTH assay (70 ng/L) revealed that mortality in this subgroup was associated with oxidized PTH but not with n-oxPTH levels.
 Conclusions: The predictive power of n-oxPTH and iPTH on the mortality of hemodialysis patients differs substantially. Measurements of n-oxPTH may reflect the hormone status more precisely. The iPTH-associated mortality is most likely describing oxidative stress-related mortality.
Y1  - 2013
U6  - https://doi.org/10.1210/jc.2013-2139
SN  - 0021-972X
SN  - 1945-7197
VL  - 98
IS  - 12
SP  - 4744
EP  - 4751
PB  - Endocrine Society
CY  - Chevy Chase
ER  -