Association between functional genetic variants in retinoid X receptor-α/γ and the risk of gestational diabetes mellitus in a southern Chinese population

To clarify the effect of retinoid X receptor-α/γ (RXR-α/γ) genes functional genetic variants (RXR-α rs4842194 G>A, RXR-γ rs100537 A>G and rs2134095 T>C) on the risk of gestational diabetes mellitus (GDM), a case-control study with 573 GDM patients and 740 pregnant women with normal glucose tolerance was performed in Guangxi area of China. An odds ratio (OR) with its corresponding 95% confidence interval (CI) was used to assess the strengths of the association between genetic variation and GDM. After adjustment of age and pre-BMI, the logistic regression analysis showed that the rs2134095 was significantly associated with GDM risk (CC vs. TT/TC: adjusted OR = 0.71, 95% CI = 0.56-0.90) in all subjects, and this result remained highly significant after Bonferroni's correction for multiple testing (P=0.004). The stratified analysis showed that rs2134095 was significantly associated with the risk of GDM among age > 30 years (adjusted OR = 0.61, 95% CI = 0.39-0.97), BMI > 22 kg/m2 (adjusted OR = 0.46, 95% CI = 0.30-0.70), systolic blood pressure (SBP) > 120 mmHg (adjusted OR = 1.96, 95% CI = 1.14-3.36), glycosylated hemoglobin A1c (HbA1c) < 6.5% (adjusted OR = 1.41, 95% CI = 1.11-1.78), TG ≤ 1.7 mmol/l (adjusted OR = 2.57, 95% CI = 1.45-4.53), TC ≤ 5.18 mmol/l (adjusted OR = 1.58, 95% CI = 1.13-2.22), high-density lipoprotein cholesterol (HDL-c) ≤ 1.5 mmol/l (adjusted OR = 1.70, 95% CI = 1.16-2.49) and low-density lipoprotein cholesterol (LDL-c) > 3.12 mmol/l (adjusted OR = 1.47, 95% CI = 1.08-2.00) subjects, under the recessive genetic model. We also found that rs2134095 interacted with age (Pinteraction=0.039), pre-BMI (Pinteraction=0.040) and TG (Pinteraction=0.025) influencing individual's genetic susceptibility to GDM. The rs2134095 T>C is significantly associated with the risk of GDM by effect of a single locus and/or complex joint gene-gene and gene-environment interactions. Larger sample-size and different population studies are required to confirm the findings.