TRPM6 and TRPM7 genetic polymorphisms, dietary magnesium, plasma magnesium, and gestational diabetes mellitus

Genetic variation in TRPM6 and TRPM7 contributes to magnesium (Mg) absorption defects. We aimed to verify the combined influence of Mg intake and these genetic polymorphisms on plasma Mg concentrations and the risk of gestational diabetes mellitus (GDM). We involved 1323 pregnant women from Tongji Maternal and Child Health Cohort. Two single nucleotide polymorphisms (SNPs) in TRPM6 (rs2274924 and rs3750425) and one SNP in TRPM7 (rs8042919) were genotyped through Asian Screening Array bead chip. Mg intake was evaluated using food frequency questionnaires before GDM diagnosis. Plasma Mg was measured using inductively coupled plasma mass spectrometry when 75 g oral glucose tolerance test was conducted to identify GDM. The summed number of mutant alleles for rs2274924 (T>C), rs3750425 (C>T) and rs8042919 (G>A) was associated with GDM risk, with an adjusted relative risk (RR) of 1.65 (95% confidence interval [CI]: 1.21, 2.23) for women with higher number of mutant alleles compared to those with fewer than two alleles. A significant interaction was observed between gene variants and Mg intake on GDM risk (P-interaction = .039). Notably, insufficient Mg intake (<370.0 mg/d) significantly decreased plasma Mg concentrations (15.34 mg/L vs 15.80 mg/L; P < .001) and increased GDM incidence (adjusted RR = 2.14; 95% CI, 1.24, 3.68) among participants with fewer mutant alleles. Sufficient Mg intake may be more beneficial to increase plasma Mg concentrations and decrease GDM risk among pregnant women with fewer mutations on TRPM6, TRPM7 gene variants.