Association Of Insulin-Like Growth Factor System Gene Polymorphisms With Gestational Diabetes Mellitus Risk

Objective:To investigate the relationship between gene polymorphisms of Insulin-1ike growth factors（IGFs）system and gestational diabetes mellitus（GDM）.Methods:A total of 835 pregnant women with GDM and 868 pregnant women without GDM were enrolled in this case-control study.General information and blood samples were collected.The Agena Mass ARRAY system was used to genotype the IGFs system loci（IGF-1:rs35747,rs35767,rs2114912,rs860598,rs855213;IGF-1R:rs2018860,rs2684761;IGF-2:rs680;IGF-2R:rs416572;IGF2BP2:rs4402960,rs1470579,rs11705701,rs6777038,rs16860234,rs7651090）.SPSS 26.0 software was used to analyze the association between the candidate SNPs and GDM susceptibility.Linkage disequilibrium and haplotype construction were performed by SHesis online software.Multifactor dimensionality reduction was used to analyze the interaction between loci.Results:1.Higher gestational age（OR=1.132,95%CI:1.101-1.164,P<0.001）,higher pre-pregnancy BMI（OR=1.515,95%CI:1.279-1.794,P<0.001）,and family history of T2DM（OR=2.531,95%CI:1.906-3.363,P<0.001）were the risk factors for GDM.The risk of GDM in women with one risk factor was 2.696 times higher than that in women without risk factor（95%CI:2.162-3.361,P<0.001）.The risk of GDM in women with two risk factors was 7.173 times higher than that in women without risk factor（95%CI:4.780-10.763,P<0.001）.The risk of GDM in pregnant women with three risk factors was 14.452 times higher than that in women without risk factor（95%CI:3.321-62.899,P<0.001）.2.The fasting plasma glucose level（5.05±0.88 mmol/L vs.4.34±0.31 mmol/L）,1 h-OGTT level（10.42±1.69 mmol/L vs.7.37±1.34 mmol/L）and 2 h-OGTT level（9.14±1.73 mmol/L vs.6.50±0.98 mmol/L）in the case group were significantly higher than those in the control group(P_all<0.001).3.There was no significant difference in the distribution of alleles and genotypes of the 15 candidate SNPs between the case group and the control group(P_all>0.05),and no significant statistical association was found between the candidate SNPs and the risk of GDM(P_all>0.05).However,the FPG level of CT genotype carriers at rs6777038 was significantly lower than that of TT genotype carriers（4.69±0.69 vs.5.03±1.57 mmol/L,P<0.01）,the 2 h-OGTT levels of CC and CT genotype carriers were significantly lower than those of TT genotype carriers（8.10±1.91、8.08±1.87vs.8.99±2.90 mmol/L,P<0.01）.4.Among pregnant women with family history of T2DM,the risk of GDM in pregnant women with GG genotype of rs2114912 was 0.467 times higher than that in those with TT genotype（95%CI:0.228-0.957,P=0.038）.In pregnant women without family history of T2DM,the risk of GDM in pregnant women with TA genotype at rs2018860 was 1.444 times higher than that in pregnant women with TT genotype（95%CI:1.076-1.937,P=0.014）.5.There were strong linkage disequilibrium among IGF-1 rs35747,rs35767,rs860598 and rs855213（D’>0.900,r²>0.850）.IGF2BP2 rs4402960,rs1470579 and rs7651090 were also in strong linkage disequilibrium（D’>0.900,r²>0.850）.6.No gene-gene interaction was found among candidate SNPs in the pathogenesis of GDM.7.There was no significant difference in serum IGF-1 and IGFBP-3 levels between the case group and the control group(P_all>0.05).Conclusions:The association between IGFs gene loci and GDM susceptibility has not been found in this study.