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Genetics of melatonin receptor type 2 is associated with left ventricular function in hypertensive patients treated according to guidelines

  • 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 withBackground: 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.show moreshow less

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Author:Matthias Huber, Andras Treszl, Rona Katharina ReibisORCiDGND, Christopher Teichmann, Irina Zergibel, Juliane Bolbrinker, Juergen Scholze, Karl WegscheiderORCiDGND, Heinz Voeller, Reinhold Kreutz
DOI:https://doi.org/10.1016/j.ejim.2013.03.015
ISSN:0953-6205 (print)
Parent Title (English):European journal of internal medicine : official journal of the European Federation of Internal Medicine
Publisher:Elsevier
Place of publication:Amsterdam
Document Type:Article
Language:English
Year of first Publication:2013
Year of Completion:2013
Release Date:2017/03/26
Tag:Clinical study; Genetics; Heart; Hypertension; Melatonin receptor type 2
Volume:24
Issue:7
Pagenumber:6
First Page:650
Last Page:655
Funder:Deutsche Hochdruckliga (DHL (R))
Organizational units:Humanwissenschaftliche Fakultät / Strukturbereich Kognitionswissenschaften
Peer Review:Referiert
Institution name at the time of publication:Humanwissenschaftliche Fakultät / Exzellenzbereich Kognitionswissenschaften