Aims: Emerging evidence suggested genetic factor attributed as a major determinant for the complex pathogenic mechanism of gestational diabetes mellitus (GDM), but the related genetic study was limited. We aimed to investigate the impact of polymorphisms in miRNA-binding sites (miR-binding SNPs) on the risk of GDM in Chinese Han pregnant women.
Methods: We screened GDM susceptibility genes extensively and selected miR-binding SNPs using four bioinformatics software. TaqMan allelic discrimination assays were applied to miR-binding SNPs genotyping in 839 GDM patients and 900 controls.
Results: In total five potential miR-binding SNPs (SLC30A8 rs2466293, INSR rs1366600, INSR rs3745550, KCNJ11 rs5210 and KCNQ1 rs8234) were selected. Our results showed that SLC30A8 rs2466293 [OR 95% CI = 1.455 (1.077, 1.966); P = 0.014] and INSR rs1366600 [OR 95% CI = 2.191 (1.077, 4.455); P = 0.029] increased the risk of GDM after adjusting age in additive model. Furthermore, rs2466293 was found to significantly associate with higher levels of fasting plasma glucose (b dom = 0.054, P dom = 0.032), 2-h OGTT plasma glucose (b dom = 0.069, P dom = 0.007), lower fasting insulin concentrations (b rec = -0.082, P rec = 0.003) and decreased HOMA-B (b rec = -0.067, P rec = 0.015). Additionally, the correlation between rs1366600 and 2-h OGTT plasma glucose (b dom = 0.078, P dom = 0.001) was observed.
Conclusions: Two miR-binding SNPs SLC30A8 rs2466293 and INSR rs1366600 increased GDM susceptibility. Functional studies were required to confirm the underlying mechanism. Our study provided additional insights into the genetic pathogenesis of GDM.
Keywords: Gestational diabetes mellitus; Glucose metabolism; Variants; miRNA.