rs1387153

Two-stage case-control study of 1,429 pregnant women in Southern China examining MTNR1B gene variants and gestational diabetes mellitus (GDM) susceptibility. SNP rs10830963 was significantly associated with increased GDM risk in the combined analysis (additive model OR=1.36, 95%CI=1.17-1.59, P<0.001; dominant model OR=1.45, 95%CI=1.15-1.83, P=0.005). The rs10830963 variant showed interaction with maternal age and BMI in contributing to GDM risk.

This comprehensive review synthesizes literature on gestational diabetes mellitus (GDM), demonstrating its complex multifactorial etiology involving genetic factors (SNPs in GCKR, KCNQ1, MTNR1B, TCF7L2), epigenetic modifications (DNA methylation and microRNA expression), and alterations in microbial composition across multiple body sites. While certain SNP variants are associated with GDM phenotypes globally, genetic predisposition alone does not explain disease development; lifestyle factors can modify epigenetic signatures and microbiota composition to modulate risk. Evidence indicates genes, epigenetic alterations, and microbiota can transfer from mother to offspring with long-term health consequences.

A case-control study of 674 GDM patients and 690 controls combined with a meta-analysis found that the G allele of rs10830963 and T allele of rs1387153 in MTNR1B are significantly associated with increased risk of gestational diabetes mellitus (GDM). Meta-analysis of 6 studies showed rs10830963 G allele increased GDM risk in co-dominant model (OR 1.62, 95% CI 1.34-1.94) and rs1387153 T allele increased risk in co-dominant model (OR 1.53, 95% CI 1.26-1.86).

This case-control study of 314 Euro-Brazilian pregnant women (134 with gestational diabetes, 180 controls) investigated the association of two polymorphisms with gestational diabetes: rs7799039 in the LEP gene and rs13266634 in the SLC30A8 gene. Neither polymorphism showed a statistically significant association with gestational diabetes (LEP rs7799039 p=0.627, SLC30A8 rs13266634 p=0.522), and genotype frequencies did not differ between groups.

Replication study in Japanese (n=4,813) and Sri Lankan (n=2,319) populations confirmed association of five common variants at four loci (GCK rs1799884, GCKR rs780094, G6PC2-ABCB11 rs560887, MTNR1B rs1387153 and rs10830963) with fasting plasma glucose levels (p<0.05). Fine-mapping identified a novel independent SNP rs3755157 in the G6PC2-ABCB11 region with stronger association (β=0.055-0.069 mmol/l, p=2.6×10⁻⁸ in Japanese) and confirmed allelic heterogeneity. Type 2 diabetes association was replicated in case-control studies (OR 1.09-1.28).

This study examined associations between rs10830963 in the MTNR1B gene and measures of insulin secretion and glucose metabolism in 1,276 healthy European individuals from the RISC study. The minor G allele was significantly associated with higher fasting glucose (beta=0.17, p=5.8×10⁻⁵) and impaired early insulin response (beta=-0.19, p=1.7×10⁻⁵), but showed no association with whole-body insulin sensitivity measured by euglycaemic-hyperinsulinaemic clamp.

This study replicated the association between rs10830963 in MTNR1B (melatonin receptor 1B) and type 2 diabetes in Han Chinese individuals, previously reported in European populations. The risk allele (G) was associated with increased type 2 diabetes risk (OR 1.16, 95% CI 1.03-1.31, p=0.015) and elevated fasting plasma glucose (0.068 mmol/l per allele, p=4×10⁻⁵), suggesting this is a cross-population effect.