ABSTRACT: OBJECTIVE:To study the associations of vascular endothelial growth factor (VEGF) expression and its gene polymorphisms with the risk of gestational diabetes mellitus (GDM). METHODS:A total of 239 GDM patients (GDM group) and 275 healthy pregnant women (Control group) were included in this study. VEGF genotypes (including rs2146323, rs2010963, rs3025039, rs3025010, and rs833069) were analyzed by TaqMan assay. ELISA was used to determine the serum VEGF levels. The software SHEsis was performed to analyze haplotypes. RESULTS:The carrier with the rs2146323 AA, CA+AA genotypes, and A allele, as well as the rs3025039 CT, TT, CT+TT genotypes, and T allele showed the increased risk of GDM (all P < 0.05), but the distributions of genotype and allele at rs2010963, rs3025010, and rs833069 were not significantly different between GDM patients and controls (all P > 0.05). Notably, the frequency of rs2010963-rs833069-rs2146323-rs3025010 haplotypes CAAC, CAAT, CACC, CACT, GACT, and GGCT was found statistically different between GDM patients and controls (all P < 0.05). The patients with rs3025039 CT+TT genotype had higher VEGF levels than those with CC genotype (all P < 0.05). Besides, age, family histories of diabetes, previous GDM, hypertension, pre-pregnancy body mass index, fasting plasma glucose, fasting insulin, homeostasis model assessment (HOMA)-IR, rs2146323 CA+AA, rs3025039 CT+TT, and VEGF expression level were independent risk factors, while HOMA-? was an independent protective factor for GDM (all P < 0.05). CONCLUSION:VEGF rs2146323 and rs3025039 polymorphisms and its expression were significantly correlated with the risk of GDM, providing a great clinical value for GDM assessment and diagnosis.