Association Of Glucokinase Gene And Glucokinase Regulatory Protein Gene Polymorphisms With Gestational Diabetes Mellitus

Objective:To investigate the association of glucokinase?GCK?gene,glucokinase regulatory protein?GCKR?gene polymorphism and gene-gene interaction with susceptibility to gestational diabetes mellitus?GDM?.Methods:A case-control study was conducted in this study.From January 2018 to March2019,pregnant women who had a positive 75g glucose tolerance test?OGTT?at the Maternal and Child Health Hospital of Hubei Province were selected as the case group of this study.In the same period and hospital,pregnant women with at most one-week difference in gestational weeks and normal OGTT were selected as the control group.The general characteristics of the study subjects were collected;their fasting venous blood was acquired,and whole blood DNA was extracted.The t/?² test and Logistic regression were used to analyze the influencing factors of GDM.The candidate SNPs?GCKR genes rs1799884,rs4607517,rs730497,rs10278336,rs2268574,and GCKR gene rs780094,rs1260326?were genotyped using the Agena MassARRAY system.The Pearson?² test was used to analyze the distribution of alleles and genotypes of SNPs between the case group and the control group.The association between SNPs polymorphism and susceptibility of GDM was analyzed by unconditional Logistic regression.The multifactor dimensionality reduction method?MDR?was used to analyze the effect of gene-gene interaction on the risk of GDM.Results:?1?Older age?OR=1.138,95%CI:1.104-1.173,P<0.001?,high BMI before pregnancy?OR=1.055,95%CI:1.015-1.097,P=0.007?,family history of diabetes?OR=2.760,95%CI:2.012-3.786,P<0.001?were risk factors for GDM,and early pregnancy response was a protective factor for GDM?OR=0.500,95%CI:0.383-0.651,P<0.001?.?2?GCK genes rs1799884,rs4607517,rs10278336,rs2268574 and GCKR genes rs780094,rs1260326 met the Hardy-Weinberg equilibrium test,and the next analyses could be performed.?3?The allele and genotype distributions of the GCK rs1799884 locus were different between the case group and the control group(P_allele=0.032;P_genotype=0.028);GCK gene rs1799884 locus in the codominant model,pregnant women carrying the TT genotype were 2.397 times more likely to develop GDM than those carrying the CC genotype?95%CI:1.304-4.395,P=0.005?;in the recessive model,pregnant women carrying the TT genotype were 2.361 times more likely to develop GDM than carriers of the TC or CC genotype?95%CI:1.294-4.307,P=0.005?;the GCK gene rs4607517 locus in the superdominant model,the GA genotype carriers were 0.735 times more likely to develop GDM than carriers of GG or AA genotypes?95%CI:0.539-1.001,P=0.051?.?4?No gene-gene interaction was found in the above candidate loci in the pathogenesis of GDM.?5?GCK gene rs1799884 polymorphism was associated with fasting blood glucose level?P=0.023?;GCK gene rs4607517 polymorphism was associated with fasting blood glucose,1-hour OGTT blood glucose,and 2-hour OGTT blood glucose levels(P_all<0.001)Conclusion:The polymorphisms of rs1799884 and rs4607517 of GCK genes were associated with susceptibility to GDM.GCKR gene rs780094 and rs1260326 were not found to be associated with GDM susceptibility.