title: Genetics of melatonin receptor type 2 is associated with left ventricular function in hypertensive patients treated according to guidelines.
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±9.4years, 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: 2.4mmHg, 95% confidence interval (CI): 0.3 to 4.5mmHg, 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Clinical Pharmacology and Toxicology, Charité-Universitätsmedizin Berlin, Berlin, Germany. Electronic address: matthias.huber@charite.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Huber
authors.forename: Andras
authors.initials: A
authors.lastname: Treszl
authors.forename: Rona
authors.initials: R
authors.lastname: Reibis
authors.forename: Christopher
authors.initials: C
authors.lastname: Teichmann
authors.forename: Irina
authors.initials: I
authors.lastname: Zergibel
authors.forename: Juliane
authors.initials: J
authors.lastname: Bolbrinker
authors.forename: Jürgen
authors.initials: J
authors.lastname: Scholze
authors.forename: Karl
authors.initials: K
authors.lastname: Wegscheider
authors.forename: Heinz
authors.initials: H
authors.lastname: Völler
authors.forename: Reinhold
authors.initials: R
authors.lastname: Kreutz
mesh_terms: D000368:Aged; D004452:Echocardiography; D005260:Female; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017410:Practice Guidelines as Topic; D044122:Receptor, Melatonin, MT1 / Q000235:genetics* / Q000378:metabolism; D044123:Receptor, Melatonin, MT2; D015398:Signal Transduction / Q000502:physiology; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000235:genetics* / Q000628:therapy*; D016277:Ventricular Function, Left / Q000235:genetics*
chemical_list: C573871:MTNR1B protein, human; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2
keywords: Clinical study; Genetics; Heart; Hypertension; Melatonin receptor type 2