Study On The Relationship Between Type 2 Diabetes Mellitus And CDKAL1 Gene,KCNQ1 Gene Polymorphism And Related Gene-Gene And Gene-Environment Interactionsina Mongolian Population

Objective Objective to investigate the life and social behavior of Mongolian people,to explore the risk factors of type 2 diabetes mellitus(T2DM)in this population,to analyze the relationship between CDKAL1 gene and KCNQ1 gene polymorphism and T2 DM by molecular epidemiological method,to find out the high-risk genotypes of CDKAL1 gene and KCNQ1 gene,and then to explore the gene gene The effect of gene environment interaction on T2 DM.Methods According to the inclusion and exclusion criteria,238 Mongolian T2 DM patients from Xincheng District,Yuquan District,Huimin district and Saihan District of Hohhot City,Zhalute banner of Tongliao City,Xilinhot City,dongwuzhumuqin banner and Zhenglan Banner of Xilinguole League from August 2018 to August 2020 were selected as the case group,238 matched healthy people in the same population were selected as the control group.Multiple high temperature ligase detection reaction(i MLDR)genotyping technology was used to genotype CDKAL1 gene SNPs rs10946398,rs35612982,rs9465871 and KCNQ1 gene SNPs rs2237892,rs2299620,rs231362.Univariate and multivariate unconditional logistic regression analysis was used to analyze environmental factors The association between gene polymorphism and Mongolian T2 DM was studied by GMDR.Results(1)There were significant differences in BMI,WHR,SBP and family history of diabetes between the case group and the control group(P<0.05).(2)FPG,TC and TG of the case group were higher than those of the control group,HDL-C was lower than that of the control group,and the difference was statistically significant(P<0.05).(3)The risk of T2 DM was 1.780 times(OR=1.780,95%CI=1.036-3.057),4.727 times(OR=4.727,95%CI=2.699-8.278)and 2.060 times(OR=2.060,95%CI=1.154-3.677),respectively,The risk of patients with family history of diabetes was 2.547 times higher than that of patients without family history of diabetes(OR=2.547,95%CI=1.514-4.286).(4)The SNPs rs10946398,rs35612982,rs9465871 of CDKAL1 gene and rs2237892,rs2299620,rs231362 of KCNQ1 gene were in accordance with the genetic balance.Genotypes of AA,CA and CC at rs10946398 of CDKAL1 gene(χ2=440,P=0.040),rs35612982 TT,CT,CC genotype(χ2=100,P=0.006),rs9465871 TT,CT,CC genotype(χ2=7.200,P=0.027).The difference of frequency distribution between the case group and the control group was statistically significant.There was no significant difference in the genotype frequency distribution of the three loci of KCNQ1 gene between the case group and the control group(P>0.05).(5)CDKAL1 rs10946398 A and C alleles(χ2=240,P=0.012),T and C alleles of rs35612982(χ2=200,P=0.001),T and C alleles of rs9465871(χ2=420,P=0.006).The risk of T2 DM was 1.39 times(OR=1.390,95%CI=1.073-1.801),1.535 times(OR=1.535,95%CI=1.180-1.997)and 1.424 times(OR=1.424,95%CI=1.103-1.839)in C allele carriers.There was no significant difference in allele frequency distribution of the three loci of KCNQ1 gene between the case group and the control group(P>0.05).(6)CDKAL1 rs10946398 CCvs.AA,CCvs.AA + CA,rs35612982 CTvs.TT,CCvs.TT,CT + CCvs.TT,CCvs.TT + CT,rs9465871 CCvs.TT,CT + CCvs.TT,CCvs.TT+ CT increased the risk of T2 DM.KCNQ1 gene is not associated with T2 DM in all genetic models.After adjusting for BMI,CDKAL1 gene rs10946398 CCvs.AA,Ca +CCvs.AA,CCvs.AA + CA,rs35612982 CCvs.TT,CT + CCvs.TT,CCvs.TT + CT,rs9465871 CCvs.TT,CCvs.TT + CT genetic model increased the risk of T2 DM.No association between KCNQ1 gene and T2 DM was found in the adjusted genetic model.(7)The three loci of CDKAL1 gene from left to right were rs10946398,rs35612982 and rs9465871(χ2=840,P=0.015),CCC haplotype(χ2=796,P=0.001).The patients with ATT haplotype had lower risk of T2DM(OR=0.880,95%CI=0.559-0.385),while the patients with CCC haplotype had higher risk of T2DM(OR=1.535,95%CI=1.173-2.009).There was no significant difference in the frequencies of CC,CT and TT haplotypes from left to right(P>0.05),and there was no association between CC,CT and TT haplotypes and T2 DM.(8)There was no significant difference in the interaction model between CDKAL1 and KCNQ1(P>0.05).(9)There were significant differences between rs10946398 of CDKAL1 gene and family history of diabetes,rs35612982 and activity intensity and family history of diabetes,rs9465871 and activity intensity and family history of diabetes,rs2299620 of KCNQ1 gene and employment and mental health(P>0.05).Conclusion(1)Family history of diabetes may be a risk factor for type 2 diabetes in Mongolian people.(2)The mutation of CDKAL1 gene rs10946398 a > C,rs35612982 t > C,rs9465871 t >C is a risk mutation in Mongolian population,which may increase the risk of T2 DM.(3)No interaction was found between CDKAL1 SNPs rs10946398,rs35612982,rs9465871 and KCNQ1 SNPs rs2237892,rs2299620,rs231362.(4)There were interactions between rs10946398 of CDKAL1 gene and family history of diabetes,rs35612982 and activity intensity and family history of diabetes,rs9465871 and activity intensity and family history of diabetes,rs2299620 of KCNQ1 gene and employment and mental health.