No association between a common type 2 diabetes risk gene variant in the melatonin receptor gene (MTNR1B) and mortality among type 2 diabetes patients

J Pineal Res. 2022 Mar;72(2):e12785. doi: 10.1111/jpi.12785. Epub 2022 Jan 8.

Abstract

The minor G risk allele in the common melatonin receptor gene (MTNR1B, rs10830963) has been associated with an increased risk of myocardial infarction among patients with type 2 diabetes (T2D). Furthermore, activating the melatonin receptor 1B through melatonin has been shown to promote cell proliferation, which could be hypothesized to increase cancer risk. Cardiovascular disease (CVD) and cancer are common causes of death among patients with T2D. Using data from 14 736 patients with T2D who participated in the UK Biobank investigation, we hypothesized an additive effect of the G risk allele on all-cause mortality, CVD mortality, and cancer mortality. As shown by Cox regression adjusted for confounders such as age, glucose-lowering medication, and socioeconomic status, no significant trend between the number of G risk alleles and mortality outcomes was found during the follow-up period of 11.1 years. Our negative findings do not speak against the role of this gene variant in the development of T2D, as repeatedly shown by previous large-scale studies. Instead, they may suggest that rs10830963 is less relevant for mortality risk in patients with T2D.

Keywords: cancer; cardiovascular disease; melatonin receptor; mortality; type 2 diabetes.

MeSH terms

  • Alleles
  • Blood Glucose / genetics
  • Blood Glucose / metabolism
  • Child
  • Diabetes Mellitus, Type 2* / genetics
  • Diabetes Mellitus, Type 2* / metabolism
  • Humans
  • Melatonin* / metabolism
  • Polymorphism, Single Nucleotide
  • Receptor, Melatonin, MT2* / genetics

Substances

  • Blood Glucose
  • MTNR1B protein, human
  • Receptor, Melatonin, MT2
  • Melatonin