Interactions of two-factor gene-gene model.

ObjectiveTo investigate the associations of Insulin-like growth factor-II (IGF2) gene, Insulin-like growth factor-II receptor (IGF2R) gene and Insulin-like growth factor-II binding protein 2 (IGF2BP2) gene polymorphisms with the susceptibility to gestational diabetes mellitus (GDM) in Chinese population.MethodsA total of 1703 pregnant women (835 GDM and 868 Non-GDM) were recruited in this case-control study. All participants underwent prenatal 75 g oral glucose tolerance test (OGTT) examinations during 24–28 gestational weeks at the Maternal and Child Health Hospital of Hubei Province from January 15, 2018 to March 31, 2019. Genotyping of candidate SNPs (IGF2 rs680, IGF2R rs416572, IGF2BP2 rs4402960, rs1470579, rs1374910, rs11705701, rs6777038, rs16860234, rs7651090) was performed on Sequenom MassARRAY platform. Logistic regression analysis was conducted to investigate the associations between candidate SNPs and risk of GDM. In addition, multifactor dimensionality reduction (MDR) method was applied to explore the effects of gene-gene interactions on GDM risk.ResultsThere were significant distribution differences between GDM group and non-GDM group in age, pre-pregnancy BMI, education level and family history of diabetes (P < 0.05). After adjusted for age, pre-pregnancy BMI, education level and family history of diabetes, there were no significant associations of the candidate SNPs polymorphisms and GDM risk (P > 0.05). Furthermore, there were no gene-gene interactions on the GDM risk among the candidate SNPs (P > 0.05). However, the fasting blood glucose (FBG) levels of rs6777038 CT carriers were significantly lower than TT carriers (4.69±0.69 vs. 5.03±1.57 mmol/L, P < 0.01), and the OGTT-2h levels of rs6777038 CC and CT genotype carriers were significantly lower than TT genotype carriers (8.10±1.91 and 8.08±1.87 vs. 8.99±2.90 mmol/L, P < 0.01).ConclusionsIGF2 rs680, IGF2R rs416572, IGF2BP2 rs4402960, rs1470579, rs11705701, rs6777038, rs16860234, rs7651090 polymorphisms were not significantly associated with GDM risk in Wuhan, China. Further lager multicenter researches are needed to confirm these results.

研究目的：探究胰岛素样生长因子-II（IGF2）基因、胰岛素样生长因子-II受体（IGF2R）基因及胰岛素样生长因子-II结合蛋白2（IGF2BP2）基因多态性与中国人群妊娠糖尿病（GDM）易感性的关联。研究方法：本项病例对照研究纳入了1703名孕妇（835例GDM和868例非GDM）。所有参与者在湖北省妇幼保健院于2018年1月15日至2019年3月31日期间，在孕24-28周期间接受了孕前75克口服葡萄糖耐量试验（OGTT）检查。在Sequenom MassARRAY平台上对候选单核苷酸多态性（SNPs）（IGF2 rs680、IGF2R rs416572、IGF2BP2 rs4402960、rs1470579、rs1374910、rs11705701、rs6777038、rs16860234、rs7651090）进行基因分型。通过逻辑回归分析探讨候选SNPs与GDM风险之间的关联。此外，采用多因素降维（MDR）方法探究基因间相互作用对GDM风险的影响。研究结果：GDM组与非GDM组在年龄、孕前体重指数、教育水平和糖尿病家族史方面存在显著差异（P < 0.05）。调整年龄、孕前体重指数、教育水平和糖尿病家族史后，候选SNPs多态性与GDM风险之间无显著关联（P > 0.05）。此外，在候选SNPs中未发现GDM风险存在基因间相互作用（P > 0.05）。然而，rs6777038 CT基因型携带者的空腹血糖（FBG）水平显著低于TT基因型携带者（4.69±0.69 vs. 5.03±1.57 mmol/L，P < 0.01），且rs6777038 CC和CT基因型携带者的口服葡萄糖耐量试验2小时（OGTT-2h）水平显著低于TT基因型携带者（8.10±1.91和8.08±1.87 vs. 8.99±2.90 mmol/L，P < 0.01）。研究结论：IGF2 rs680、IGF2R rs416572、IGF2BP2 rs4402960、rs1470579、rs11705701、rs6777038、rs16860234、rs7651090多态性与武汉地区GDM风险无显著关联。为进一步验证这些结果，需要开展更大规模的多中心研究。