Association of one-carbon metabolism-related nutrients with gestational diabetes mellitus stratified by MTNR1B polymorphisms in Chinese populations

This study aimed to explore the associations of melatonin receptor 1B (MTNR1B) genetic variants with gestational diabetes mellitus (GDM) and to examine how MTNR1B single-nucleotide polymorphisms (SNPs) might influence the association between one-carbon metabolism (OCM)-related nutrients and GDM. This cross-sectional study analyzed 1,254 pregnant women for three SNPs (rs1387153, rs10830962, and rs10830963) in MTNR1B, as well as serum folate and vitamin B 12 . Logistic regression was used to assess the associations of these SNPs and OCM‑related nutrients with GDM risk. Fasting and 1-hour plasma glucose significantly differed among genotypes at all three SNPs, but 2-hour plasma glucose did not. MTNR1B rs1387153 (CT/TT vs. CC, OR = 1.52; 95% CI, 1.10–2.09; P FDR = 0.027) was associated with GDM. Among carriers of the rs1387153 T allele, higher serum folate (OR = 2.10; 95% CI, 1.15–3.85; P FDR = 0.048), lower serum vitamin B 12 (OR = 2.22; 95% CI, 1.24–3.98; P FDR = 0.036), and higher folate/vitamin B 12 ratio (OR = 2.57; 95% CI, 1.41–4.68; P FDR = 0.018) had significantly higher GDM risk compared with CC homozygotes. Our findings preliminarily suggest that the MTNR1B rs1387153 polymorphism is associated with susceptibility to GDM in the Chinese population. Notably, exploratory stratified analyses suggested different associations between OCM-related nutrient profiles and GDM across MTNR1B genotype subgroups, although formal interaction tests were not statistically significant.