Abstract
BackgroundsTwo SNPs in melatonin receptor 1B gene, rs10830963 and rs1387153 showed significant associations with fasting plasma glucose levels and the risk of Type 2 Diabetes Mellitus (T2DM) in previous studies. Since T2DM and gestational diabetes mellitus (GDM) share similar characteristics, we suspected that the two genetic polymorphisms in MTNR1B may be associated with GDM, and conducted association studies between the polymorphisms and the disease. Furthermore, we also examined genetic effects of the two polymorphisms with various diabetes-related phenotypes.MethodsA total of 1,918 subjects (928 GDM patients and 990 controls) were used for the study. Two MTNR1B polymorphisms were genotyped using TaqMan assay. The allele distributions of SNPs were evaluated by x2 models calculating odds ratios (ORs), 95% confidence intervals (CIs), and corresponding P values. Multiple regressions were used for association analyses of GDM-related traits. Finally, conditional analyses were also performed.ResultsWe found significant associations between the two genetic variants and GDM, rs10830963, with a corrected P value of 0.0001, and rs1387153, with the corrected P value of 0.0008. In addition, we also found that the two SNPs were associated with various phenotypes such as homeostasis model assessment of beta-cell function and fasting glucose levels. Further conditional analyses results suggested that rs10830963 might be more likely functional in case/control analysis, although not clear in GDM-related phenotype analyses.ConclusionThere have been studies that found associations between genetic variants of other genes and GDM, this is the first study that found significant associations between SNPs of MTNR1B and GDM. The genetic effects of two SNPs identified in this study would be helpful in understanding the insight of GDM and other diabetes-related disorders.
Highlights
The prevalence of type 2 diabetes mellitus (T2DM) in Korean population has dramatically increased over last decades
Most of the phenotypes investigated for the subjects showed significant difference between the Gestational diabetes mellitus (GDM) patients group and the control group, (Table 1, P value < 0.0001 for all phenotypes except mean gestational week), which was to be expected because the phenotypes that showed the significant differences were associated with the diabetic condition
We first performed association analyses of the two genetic polymorphisms in GDM and non-GDM subjects to determine whether these polymorphisms were associated with a higher risk of developing GDM, which were previously found to be associated with T2DM, with the risk of GDM (Table 2)
Summary
The prevalence of type 2 diabetes mellitus (T2DM) in Korean population has dramatically increased over last decades. Asian populations traditionally had a low percentage of T2DM patients, it has increased drastically in recent decades. This is largely due to the fact that Asian countries are adopting western lifestyle and diets. Gestational diabetes mellitus (GDM) is a condition in which pregnant women exhibit glucose intolerance in various degrees [2], affecting approximately 2-14% of pregnancies [1,3,4]. Women with GDM show similar physiological and genetic characteristics found in diabetes outside of pregnancy, and not surprisingly, women with GDM possess higher risk for developing T2DM when they are not pregnant. Studying GDM is a good way to study early pathogenesis of diabetes and possibly develop treatment or remedy for the disease [5]
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