Homozygous AA Genotype of IL-17A and 14-bp Insertion Polymorphism in HLA-G 3′UTR Are Associated with Increased Risk of Gestational Diabetes Mellitus

Gestational diabetes mellitus (GDM) is a common pregnancy complication characterized by hyperglycemia and insulin resistance, with unclear genetic mechanisms. The specific involvement of proinflammatory cytokines, including IL-17A, and the immuno-tolerogenic HLA-G remains poorly understood in GDM. We aimed to explore the associations of three polymorphisms, <i>IL-17A</i> -197G>A (rs2275913), <i>IL-17RA</i> -947A>G (rs4819554), and HLA-G 14-bp insertion/deletion (indel), with GDM risk in a Brazilian population. We conducted a case-control study (79 GDM cases and 79 controls). Genetic polymorphisms were analyzed using PCR-RFLP, with DNA extracted using the Salting-out procedure. Significant associations were identified between -197G>A rs2275913 and HLA-G 14-bp indel polymorphisms in both codominant and recessive models. The <i>IL-17A</i> rs2275913 AA genotype was associated with a nearly ten-fold increased risk of GDM in both the codominant (<i>p</i> = 0.021, OR 9.89, 95% CI: 1.63-59.92) and recessive models (<i>p</i> = 0.006, OR 9.33, 95% CI: 1.57-55.38). Similarly, the HLA-G 14-bp Ins/Ins genotype was associated with an increased risk in both the codominant (<i>p</i> = 0.026, OR 3.34, 95% CI: 0.98-11.41) and recessive models (<i>p</i> = 0.010, OR 4.20, 95% CI: 1.36-12.96). <i>IL-17RA</i> polymorphism showed no significant associations. The study findings highlight the potential genetic and immune factors associated with GDM, particularly the -197G>A rs2275913 and HLA-G 14-bp indel polymorphisms. Further functional characterization is warranted to uncover the mechanism of genotype-phenotype association.