Relationships of SLC2A4, RBP4, PCK1, and PI3K Gene Polymorphisms with Gestational Diabetes Mellitus in a Chinese Population

Abstract

Background. Solute carrier family 2 member 4- (SLC2A4-) retinol binding protein-4- (RBP4-) phosphoenolpyruvate carboxykinase 1 (PCK1)/phosphoinositide 3-kinase (PI3K) is an adipocyte derived “signalling pathway” that may contribute to the pathogenesis of type 2 diabetes mellitus (T2DM). We explored whether single nucleotide polymorphisms (SNPs) of these “signalling pathway” genes are associated with gestational diabetes mellitus (GDM). Methods. Case-control studies were conducted to compare GDM and control groups. A total of 334 cases and 367 controls were recruited. Seventeen candidate SNPs of the pathway were selected. Chi-square tests, logistic regression, and linear regression were used to estimate the relationships of SNPs with GDM risk and oral glucose tolerance test (OGTT), fasting insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) levels. Model-based multifactor dimensionality reduction was used to estimate the adjusted interactions between genes. Regression and interaction analyses were adjusted by maternal age, prepregnancy BMI, and weekly BMI growth. The Bonferroni correction was applied for multiple comparisons. Results. RBP4 rs7091052 was significantly associated with GDM risk. SLC2A4 rs5435, RBP4 rs7091052, PCK1 rs1042531 and rs2236745, and PIK3R1 (coding gene of the PI3K P85 subunit) rs34309 were associated with OGTT, fasting insulin, and HOMA-IR levels in the linear regression analysis. The gene-gene interaction analysis showed that, compared with pregnant women with other genotype combinations, women with SLC2A4 rs5435 (CC/CT), RBP4 rs7091052 (CC), PCK1 rs1042531 (TT/TG) and rs2236745 (TT), and PIK3R1 rs34309 (AA) had lower GDM risk. Conclusion. SLC2A4, RBP4, PCK1, and PIK3R1 genes may be involved in the pathogenesis of GDM.