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

MTNR1B 基因多态性作为妊娠期糖尿病的危险因素:单一三级医疗中心的病例对照研究

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作者:Khalid Khalaf Alharbi, Abdulrahman Mohammed Al-Sulaiman, Khalid Muath Bin Shedaid, Ali M Al-Shangiti, Mohammed Marie, Yazeed A Al-Sheikh, Imran Ali Khan

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

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.

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.

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