MTNR1B genetic polymorphisms as risk factors for gestational diabetes mellitus: a case-control study in a single tertiary care center

Ann Saudi Med. 2019 Sep-Oct;39(5):309-318. doi: 10.5144/0256-4947.2019.309. Epub 2019 Oct 3.

Abstract

Background: Gestational diabetes mellitus (GDM) is a metabolic disease in pregnancy that causes carbohydrate intolerance and hyper-glycemia. Genome-wide association studies and meta-analyses have found that the single nucleotide polymorphisms (SNPs) rs1387153 and rs10830963 of the melatonin receptor 1B ( MTNR1B) gene are associated with GDM. No studies on the MTNR1B gene effect on GDM have been performed in Saudis, other Arabs, or other Middle Eastern populations.

Objectives: Investigate the association of genotype or allele frequencies of the two SNPs with GDM and with clinical parameters related to GDM.

Design: Case-control study.

Settings: Tertiary care center, Riyadh.

Patients and methods: We recruited 400 pregnant Saudi women ages 18-45 years (200 were diagnosed with GDM, and 200 were healthy controls). Biochemical assays were performed, and rs1387153 and rs10830963 polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism analysis and real-time polymerase chain reaction with TaqMan genotyping.

Main outcome measures: The association of MTNR1B gene (rs1387153 and rs10830963 polymorphisms) with GDM and with biochemical parameters related to GDM.

Sample size: 200 GDM cases and 200 non-GDM controls.

Results: Differences in allele frequencies for GDM vs non-GMD were statistically significant or nearly significant for both SNPs after adjustment for age and body mass index. In a logistic regression analysis, genotype TT was positively associated with post-prandial blood glucose (P=.018), but other associations were not statistically significant.

Conclusion: The odds ratios for the associations between the rs1387153 and rs10830963 SNPs and GDM exceeded 1.5-fold, which is higher than typically reported for diseases with complex genetic background. These effect sizes for GDM suggest pregnancy-specific factors related to the MTNR1B risk genotypes.

Limitations: Only two SNPs were studied.

Conflict of interest: None.

MeSH terms

  • Adolescent
  • Adult
  • Case-Control Studies
  • Diabetes, Gestational / epidemiology*
  • Diabetes, Gestational / genetics
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Pregnancy
  • Receptor, Melatonin, MT2 / genetics*
  • Risk Factors
  • Saudi Arabia / epidemiology
  • Tertiary Care Centers
  • Young Adult

Substances

  • MTNR1B protein, human
  • Receptor, Melatonin, MT2

Grants and funding

None.