Association Analysis Of 8 Snps Of CD40 And CD40LG Genes With Coronary Heart Disease And Prediction Model Construction

Objective: 1.To explore the association of 8 SNPs of CD40 and CD40 LG genes with coronary heart disease(CHD)and sudden cardiac death caused by CHD,and to construct prediction model of CHD,to provide experimental basis for forensic diagnosis and prevention of CHD and sudden cardiac death cause of CHD.Methods: 1.Used db SNP database,combined with literature,8 SNPs with high frequency of secondary alleles in CD40 and CD40 LG genes were identified as the research objects;2.Blood samples collected from autopsy in 2017-2018 from the forensic forensic center of Guizhou Medical University,They were divided into coronary heart disease group(n = 138)and control group(n = 192).The CHD group was further divided into two groups: sudden cardiac death caused by CHD group(n =62)and simple CHD group(n = 76).The relevant baseline data were collected for subsequent analysis.3.Multiple amplification and high-throughput sequencing were used to obtain genotypes.Cutadapt(v 1.2.1)and PRINSEQ-lite(v 0.20.3)were used for quality control.BWA(V 0.7.13-r1126)was used to calculate the genotypes of the target loci.Finally,Annovar(2018-04-16)was used to annotate the mutated loci.4.The differences of baseline data between CHD group and control group were compared by t-test and chi square test,Logistic regression was used to evaluate the risk value of each variable in CHD and sudden cardiac death caused by CHD.Stratified analysis was performed in the pure CHD group and sudden cardiac death caused by CHD group.5.The prediction model of CHD was established by binary logistic algorithm,and the working characteristic curve,calibration chart and decision curve of subjects were drawn to evaluate the application value of the prediction model.Results: Compared with CHD group,the risk of CHD in control group was higher in CT,TT genotype of rs1535045,CT and TT genotype of rs4239702,GT andTT genotype of rs4810485,and lower in CT and TT genotype of rs1883832.There was no significant correlation between rs1126535,rs3092923,rs3092927,rs3092929 and CHD in CD40 LG gene.2.The results showed that the T allele of rs1535045 was positively correlated with sudden cardiac death caused by CHD(OR= 2.333,P =0.01).After stratified analysis,it was found that there were different results when Gensini score? 10(OR= 2.50,P = 0.013)and Gensini score > 10(OR = 1.07,P =0.91).3.The prediction model of CHD was constructed with SNP and risk factors,including rs4810485,gender,age,BMI,left ventricular thickness,hypertension,chronic liver disease and smoking history,and presented in the form of nomogram.Conclusion: 1.The polymorphisms of rs1535045,rs1883832,rs4239702 and rs4810485 in CD40 gene are related to the occurrence of CHD,and the T allele of rs1535045 is the risk factor of sudden cardiac death caused by CHD.2.There was no significant correlation between rs1126535,rs3092923,rs3092927,rs3092929 and CHD in CD40 LG gene.3.Preliminary construction of CHD prediction model by SNP and retrospective analysis.