- 作者：Matthias Huber ; Andras Treszl ; Rona Reibis ; Christopher Teichmann ; Irina Zergibel ; Juliane Bolbrinker ; J¨¹rgen Scholze ; Karl Wegscheider ; Heinz V?ller ; Reinhold Kreutz
- 关键词：Clinical study ; Genetics ; Heart ; Hypertension ; Melatonin receptor type 2
- 刊名：European Journal of Internal Medicine
- 出版年：2013
- 出版时间：October, 2013
- 年：2013
- 卷：24
- 期：7
- 页码：650-655
- 全文大小：217 K
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 ¡À 9.4 years, 82.3 % male) with arterial hypertension and cardiac ejection fraction (EF) ¡Ý 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 ¡À 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.