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MTNR1B genetic polymorphisms as risk factors for gestational diabetes mellitus: a case-control study in a single
Khalid Khalaf Alharbi1, Abdulrahman Mohammed Al-Sulaiman2, Khalid Muath Bin Shedaid1
1From the Department of Clinical Laboratory Sciences, King Saud University, Riyadh, Saudi Arabia.
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.
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