The Associate Between Let-7 Single Nucleotide Polymorphisms And Susceptibility To Type 2 Diabetes Mellitus

Objective:To investigate the relationship between microRNA let-7 single nucleotide polymorphism?rs13293512,rs10877887?and the susceptibility to type 2 diabetes mellitus?T2DM?.Methods:A total of 356 patients with type 2 diabetes mellitus?T2DM?who were admitted to the endocrinology department of the first affiliated hospital of China medical university from August 2016 to December 2018 and were diagnosed for the first time without treatment were collected as the case group.The diagnostic criteria were fasting blood glucose?FPG??7.0mmol/L,or oral glucose tolerance test?OGTT-2h?glucose?11.1mmol/L.A total of 358 non-T2DM patients who were matched in gender and age in the community physical examination were selected as the control group.General data,clinical data and biochemical data were collected.5ml of fasting venous blood was collected from all subjects,and the whole blood genomic DNA was extracted by phenol chloroform method.The single nucleotide polymorphism of let-7 gene was detected by Mass ARRAY nucleic acid mass spectrometry.SPSS 22.0 software was used for data analysis.Chi-square test was used to verify the compatibility of alleles with the Hardy-Weinberg equilibrium?HWE?in the control group.Univariate and multivariate logistic regression analysis was used to analyze the effects of different genotypes in let-7polymorphism on the susceptibility to T2DM.Further stratified analysis was carried out according to gender,age and other factors.Multiple logistic regression analysis was used to analyze the relationship between the interaction between SNP-SNP genotypes and the susceptibility to T2DM.Results:1.The relationship between microRNA let-7 single nucleotide polymorphism rs13293512,rs10877887 and susceptibility to T2DM?1?After adjusting for gender age and BMI,the susceptibility to T2DM was increased in CC genotype carriers compared with let-7 rs13293512 wild genotype TT?CC vs TT:OR=1.241,95%CI=1.002-1.537,P=0.048?.The susceptibility to T2DM was increased in the population with TC+CC genotype in the dominant model?TC+CC vs TT:OR=1.190,95%CI=1.013-1.399,P=0.034?.Compared with allele T,C allelic carriers were more susceptible to T2DM?C vs T:OR=1.120,95%CI=1.009-1.244,P=0.003?.?2?After adjusting for confounding factors such as gender,age,smoking,alcohol consumption and BMI,it was found that compared with let-7 rs10877887 wild type TT,the T2DM susceptibility of CC genotype group was lower?CC vs TT:OR=0.779,95%CI=0.609-0.997,P=0.047?.2.Stratification of the relationship between microRNA let-7 single nucleotide polymorphism rs13293512,rs10877887 and susceptibility to T2DM?1?Stratified the included population according to factors such as gender,age,smoking,alcohol consumption and BMI,let-7 rs13293512 increased the risk of T2DM in men?CC vs TT:OR=1.941,95%CI=1.043-3.612,P=0.036?;C vs T:OR=1.357,95%CI=1.013-1.818,P=0.040).The susceptibility to T2DM increased in the study population over 55 years old?TC vs TT:OR=1.792,95%CI=1.092-2.941,P=0.021;CC vs TT:OR=2,768,95%CI=1.419-5.400,P=0.003;TC+CC vs TT:OR=1.993,95%CI=1.246-3.187,P=0.004;C vs T:OR=1.651,95%CI=1.205-2.261,P=0.002?.However,there is no statistical significance in the inclusion of female and younger than 55 years old?P>0.05?.?2?Stratified the included population according to factors such as gender,age,smoking,alcohol consumption and BMI,let-7 rs10877887 reduced the risk of T2DM in people younger than 55 years old?CC vs TT:OR=0.404,95%CI=0.192-0.849,P=0.017;C vs T:OR=0.717,95%CI=0.526-0.978,P=0.036?.However,there was no statistical significance in female and over 55 years old?P>0.05?.3.Association analysis of the interaction between polymorphisms of let-7 rs13293512 and rs10877887 in the risk of T2DM?1?There was no interaction was found between let-7 rs13293512 genotype and rs10877887 genotype(P _interaction>0.05).?2?As the number of risk genotypes increase of let-7,the susceptibility to T2DM increased(P _trend 0.057,0.049 and 0.01,respectively).4.Association analysis of the interaction among polymorphisms of let-7 rs13293512,rs10877887 and environmental risk factors in the risk of T2DM?1?There was an interaction between let-7 rs13293512 genotype CC and age factors,increasing the susceptibility to T2DM in patients over 55 years old who were included in the study(CC vs TT:OR=2.966,95%CI=1.231-7.146,P _interaction=0.015).?2?There was an interaction between let-7 polymorphism rs13293512 TC+CC genotype and age,increasing the susceptibility to T2DM in the included population over 55 years old(TC+CC vs TT:OR=1.939,95%CI=1.014-3.705,P _interaction=0.045).Conclusions:1.The results of a single polymorphism study suggest that let-7 single nucleotide polymorphism rs13293512 may be associated with increased susceptibility to T2DM.It also increases the risk of T2DM in men and people over 55 years old.2.The results of a single polymorphism study suggest that let-7 single nucleotide polymorphism rs10877887 may be associated with reduced susceptibility to T2DM.It also reduces the risk of T2DM in men and men younger than 55 years old.3.The results of SNP-SNP interaction showed that there was no significant interaction between let-7 rs13293512 and rs10877887.However,let-7 rs13293512 and rs10877887had a cumulative effect on increased susceptibility to T2DM.4.There was an interaction between let-7 rs13293512 and age factors,increasing the susceptibility to T2DM in patients over 55 years old who were included in the study.