Abstract
BACKGROUND: Although the association between HHEX, IGF2BP2, and FTO polymorphisms and the risk of GDM has been investigated in several studies, the findings have been inconsistent across different populations. The study aimed to investigate the association between genetic polymorphisms and GDM risk in a Chinese population. METHODS: 502 control volunteers and 500 GDM patients were enrolled. IGF2BP2 rs11705701 and rs4402960, FTO rs9939609, and HHEX rs1111875 and rs5015480 were all genotyped using the SNPscan™ genotyping assay. The independent sample t-test, logistic regression, and chi-square test were used to assess the variations in genotype and allele and their relationships with the risk of GDM. The blood glucose level, gestational week of delivery, and newborn weight were compared using a one-way ANOVA. RESULTS: After adjusting for confounding factors, the results show that the rs1111875 heterozygous (OR=1.370; 95% CI: 1.040-1.805; P = 0.025) and overdominant (OR=1.373; 95% CI: 1.049-1.796; P = 0. 021) models are significantly associated with an increased risk of GDM, especially for the age ≥ 30 years group: heterozygote (OR=1.646; 95% CI: 1.118-2.423; P=0.012) and overdominant (OR=1.553; 95% CI: 1.064-2.266; P = 0.022) models. In the age ≥ 30 years, the rs5015480 overdominant model (OR=1.595; 95% CI: 1.034-2.459; P = 0.035) and the rs9939609 heterozygote model (OR=1.609; 95% CI: 1.016-2.550; P=0.043), allele (OR=1. 504; 95% CI: 1.006-2.248; P = 0.047), dominant model (OR=1.604; 95% CI: 1.026-2.505; P = 0.038), and overdominant model (OR=1.593; 95% CI: 1.007-2.520; P = 0.047) were associated with a significantly increased risk of GDM; Additionally, people with the TC genotype of rs1111875 had a substantially higher 1-hour blood glucose level than TT genotype (P < 0.05). The results of the meta-analysis showed that the A allele of rs11705701 was associated with an increased risk of diabetes mellitus (P < 0.05). CONCLUSION: The study indicates that the TC genotype of rs1111875 is linked to a higher risk of GDM, particularly in women aged 30 years or older. Additionally, rs5015480 and rs9939609 were significantly associated with GDM in the same age group. These SNPs may therefore be more closely linked to GDM in older mothers.