GLIS3 rs7034200 and ADRB3 rs4994 genetic variants associated with an increased risk of gestational diabetes mellitus in Chinese women: a case-control study.

BACKGROUND: Gestational diabetes mellitus (GDM) has a complicated pathophysiology originating from interactions between susceptibility genes and adverse environmental factors. The transcription factor GLI-similar 3 (GLIS3) rs7034200C/A and adrenergic receptor beta 3 (ADRB3) rs4994T/C (Trp64Arg) polymorphisms are closely related to glucolipid metabolism, insulin resistance, obesity, and increased risk of type 2 diabetes. However, the association of these two polymorphisms with GDM in Chinese remains unknown. Therefore, this study explored the relationship between these two genetic variants and the risk of GDM, and assessed the effects of genotypes on glucolipid metabolism, oxidative stress, and clinical indicators. METHODS: This case-control study included 701 women with GDM and 1034 controls. The rs7034200C/A and rs4994T/C variants were genotyped using polymerase chain reaction-restriction fragment length polymorphism method. Clinical and biochemical parameters were analyzed. RESULTS: The GLIS3 rs7034200C/A polymorphism was associated with an elevated risk of GDM according to the genotype, allele, dominant, and recessive genetic models (P < 0.05). After correcting for maternal age, pre-pregnancy BMI, and gestational age at sampling, the dominant and recessive models retained statistical significance in the binary logistic regression models (odds ratio [OR] = 1.268 and 1.334, 95% confidence interval [CI]: 1.017-1.580 and 1.020-1.745, respectively; P < 0.05) ; the AA genotype showed a higher risk for GDM, with the CC genotype as the reference, in a multinomial logistic regression model (OR = 1.519, 95% CI: 1.120-2.061; P = 0.007). No significant discrepancies were observed in the ADRB3 rs4994T/C polymorphism based on different genetic models (P > 0.05). However, the AA/TT combined genotype of the GLIS3 rs7034200C/A and ADRB3 rs4994T/C polymorphisms was associated with an elevated risk of GDM, with the CC/TT combined genotype as a reference (OR = 1.708, 95% CI: 1.191-2.450; P = 0.004). Furthermore, the GLIS3 rs7034200C/A variant significantly affected oxidative stress, insulin resistance, and glucolipid metabolism. CONCLUSIONS: The A allele and AA genotype of the GLIS3 rs7034200C/A polymorphism, along with the AA/TT combined genotype of the GLIS3 rs7034200C/A and ADRB3 rs4994T/C variants, are genetic risk factors for GDM in Chinese women.