Association of Glucose-Dependent Insulinotropic Polypeptide Receptor Polymorphisms rs3848460 and rs3895874 with the Risk of Gestational Diabetes Mellitus

Background: This study aimed to examine the relationship between glucose-dependent insulinotropic polypeptide (GIP) polymorphisms rs3848460 and rs3895874 and the development of gestational diabetes mellitus (GDM) in Asian women. GIP, a hormone that stimulates insulin secretion and inhibits glucagon release, can be impacted by genetic variations, resulting in a reduced insulin response and elevated blood sugar levels that contribute to the development of GDM. To the best of our knowledge, only a limited number of studies have been conducted on the association between GIP gene polymorphisms and GDM. Methods: The SNPscanTM genotyping assay was employed to genotype rs3848460 and rs3895874, with 502 control participants and 500 GDM patients selected for the study. ANOVA, T-test, chi-square test, logistic regression, and various other statistical tests were employed to investigate variations in genotypes and alleles and their associations with the risk of GDM. Results: In this study, significant differences were found in pre-BMI, age, systolic blood pressure, diastolic blood pressure, and parity between GDM and healthy subjects (P < 0.05). In the codominant model, GIP rs3848460 showed a significant association with an increased risk of GDM after adjusting (GG vs. AA: OR = 1.717; 95% CI: 1.070-2.754; P = 0.025. The recessive model GG vs. AG+AA suggests an elevated risk of GDM (adjusted OR of 1.635), with P =0.034. The GG genotype and G allele demonstrated a statistically significant increased risk with an adjusted OR of 1.760 (P =0.026) and an adjusted OR of 1.250 (P =0.029), respectively. The GG genotype and G allele were found to be associated with an increased risk of GDM in GIP rs3848460. Conversely, the risk of GDM was significantly lower in the dominant model (AA+GA vs. GG: OR = 0.605; 95% CI: 0.376-0.974; P = 0.039) for GIP rs3895874. The AA genotype and A allele were correlated with a decreased risk of GDM in GIP rs3895874 after adjustment with an OR of 0.803 (P =0.032). Conclusion: GIP rs3848460 was found to be significantly associated with the risk of GDM. Conversely, the risk of GDM was significantly lower in rs3895874.