Genetic Polymorphisms Of Adiponectin Signaling Pathway And Risk Of Gestational Diabetes Mellitus

Objetive:The purpose of the present study was to investigate the relationship between adiponectin signaling pathway gene polymorphism and the risk of gestational diabetes,and provide the strategies for the prevention of gestational diabetes mellitus.Methods:Participants:We selected 334 cases of GDM pregnant women admitted to the Taiyuan birth cohort from March 1,2012 to July 30,2014,and matched 334 controls by the the same age,the place of residence was consistent,and the pregnancy time was not more than 3 months in non-GDM pregnant women.13 cases and 13 controls were excluded due to low genotyping rate.A total of 321 cases and 321 control pregnant women were included in the study.Experimental methods:We collected blood samples from pregnant women,DNA was extracted and genotyped using by Illumina Goldengate Platform.Statistical methods:Statistical analysis was performed on the R3.5.1,PLINK1.7 and SAS 9.4 software.Quantitative data were compared between groups using t test or variance analysis;qualitative data were compared between different groups using chi-square test.Associated with the GDM gene level analysis test to evaluate the use of min P;polymorphic site assessment relationship with the incidence of GDM risk gene,Logistic regression model to calculate OR and 95%CI;monomer constructed using software Haploview4.2 Domain,SAS 9.4 software was used to analyze the relationship between monomer domains and the risk of GDM.Results:The general demographic characteristics of the subjects showed that there was a statistically significant difference in the distribution of pre-pregnancy BMI and gestational weeks between the case group and the control group.Compared with the control group,the case group was given gestational weeks earlier,and more pregnant women were overweight and obese.The age of pregnant women,monthly income per capita,education level,weight gain during pregnancy,passive smoking of pregnant women and family history of chronic disease were evenly distributed in the case and control group,and the difference was not statistically significant.In the adiponectin signaling pathway-related genes,it was found that the CPT1A gene at the gene level is associated with the risk of GDM.The CPT1A gene rs2846194 and rs2602814 locus A alleles were associated with a reduced risk of GDM,and pregnant women carrying the rs2846194 locus AA genotype?OR=0.46,95%CI:0.23-0.89?compared with pregnant women carrying the GG genotype.The risk of onset was reduced by 54%,and the incidence of GDM in pregnant women with rs2602814 polymorphism AA genotype?OR=0.52,95%CI:0.33-0.82?and CA or AA genotype?OR=0.64,95%CI:0.44-0.92?The risk was 0.52 and 0.64 times that of pregnant women with CC genotype,and the risk of GDM decreased with the increase of the A allele(P_trend=0.005).The G allele of the rs59506005 locus of CPT1A gene is associated with an increased risk of GDM,carrying the CG genotype of rs59506005?OR=1.74,95%CI:1.24-2.45?and the CG or GG genotype?OR=1.65,95%CI:1.19-2.28?The risk of GDM in pregnant women is 1.74 times and 1.65 times higher than that of pregnant women with CC genotype,and the risk of GDM increases with the increase of G allele(P_trend=0.016).The ACACB gene rs10778656,rs4964745,rs4964750,rs11114053,rs3916981,and rs11114066 site mutations are associated with a reduced risk of developing GDM.The risk of GDM in pregnant women carrying the rs10778656 AG genotype?OR=0.60,95%CI:0.43-0.85?and the AG or GG genotype?OR=0.66,95%CI:0.48-0.91?was carried by pregnant women carrying the AA genotype.0.60and 0.66 times,the risk of GDM in pregnant women carrying rs4964745 GA genotype?OR=0.61,95%CI:0.43-0.86?and GA or AA genotype?OR=0.66,95%CI:0.48-0.92?was Pregnant women carrying GG genotype were 0.61 and 0.66 times,carrying rs4964750 AG genotype?OR=0.61,95%CI:0.43-0.86?and AG or GG genotype?OR=0.66,95%CI:0.48-0.92?pregnant women The risk of GDM is 0.61 and 0.66times higher than that of pregnant women carrying AA genotype,carrying rs11114053GA genotype?OR=0.63,95%CI:0.45-0.88?and GA or AA genotype?OR=0.68,95%CI:0.49-0.93?The risk of GDM in pregnant women is 0.63 and 0.68 times higher than that of pregnant women with GG genotype,carrying rs3916981 AG genotype?OR=0.60,95%CI:0.42-0.84?and AG or GG genotype?OR=0.66,95%CI:0.48-0.91?The risk of GDM in pregnant women is 0.60 and 0.66 times higher than that of pregnant women carrying AA genotype,carrying rs11114066 AG genotype?OR=0.66,95%CI:0.45-0.95?and AG Or GG genotype?OR=0.69,95%CI:0.48-0.97?.The risk of GDM in pregnant women is 0.66 and 0.69 times higher than that of pregnant women with AA genotype.The G allele of the rs2270033 locus of ADIPOR2 gene is associated with an increased risk of GDM,carrying the rs2270033 locus AG genotype?OR=1.47,95%CI:1.05-2.05?and the AG or GG genotype?OR=1.39,95%CI:1.02-1.92?The risk of GDM in pregnant women is 1.47 times and 1.39 times that of pregnant women carrying AA genotype.In the RXRG gene rs79617888 and rs12088020 site mutations are associated with increased risk of GDM,the risk of GDM in pregnant women carrying the rs79617888site CC genotype?OR=7.81,95%CI:2.05-51.45?is 7.81 times higher than that of pregnant women carrying GG genotype.With the increase of C allele,the risk of GDM increased(P_trend=0.019),carrying the polymorphism site rs12088020 GG genotype?OR=8.28,95%CI:2.20-54.23?and AG or GG genotype?OR=1.45,95%CI:1.01-2.09?The risk of GDM in pregnant women was 8.28 and 1.45 times higher than that of pregnant women with AA genotype,and the risk of GDM increased with the increase of G allele(P_trend=0.007).There are two haplotype?CPT1A rs2846194 rs2846207 rs2602820 rs2602814rs2846199?and?CPT1A rs1249582 rs12803642 rs59506005 rs2513102 rs2846196?in the CPT1Agene.AACAG haplotype?OR=0.75,95%CI:0.45-0.98?and ACGGA haplotype?OR=0.74,95%CI:0.44-0.93?in the CPT1A gene is associated with a reduced risk of developing GDM.In the monomeric domain of the RXRG gene?RXRG rs3753897 rs79617888 rs73022927 rs438891 rs12088020 rs10918192rs878180 rs285428?,the CCACGGAA haplotype was associated with a reduced risk of GDM?OR=0.75,95%CI:0.48-0.91?.Conclusions:For the first time,we found that the ACACB,ADIPOR2,CPT1A and RXRG gene polymorphisms were associated with the risk of GDM.GDM risk associated with the haplotype CPT1A?rs2846194 rs2846207 rs2602820 rs2602814 rs2846199?and?rs1249582 rs12803642 rs59506005 rs2513102 rs2846196?,the haplotype in RXRG gene?rs3753897 rs79617888 rs73022927 rs438891 rs12088020 rs10918192 rs878180rs285428?is related to the risk of GDM.