The Correlation Analysis Between Single Nucleotide Polymorphisms Of CEACAM5 Gene And Dilated Cardiomyopathy

Objectives:1.To investigate the correlation between single nucleotide polymorphisms(SNP)of carcinoembryonic antigen-related cell adhesion molecule 5(CEACAM5)gene and genetic susceptibility to dilated cardiomyopathy(DCM).2.To explore the relationship between SNP of CEACAM5 gene and B-type brain natriuretic peptide(BNP),New York Heart Associaton(NYHA)classification of cardiac function,and Cardiac ultrasound parameter in DCM patients.Methods:1.A case-control study was used in this study.A total of 47 patients diagnosed with DCM hospitalized in the Department of Cardiology,the First Affiliated Hospital of Kunming Medical University from 2018 to 2020,were selected as the case group,and 14 healthy people who underwent physical examination in the physical examination center of the First Affiliated Hospital of Kunming Medical University in the same period as the control group.All the subjects were independent individuals.Genomic DNA was extracted from peripheral blood of 47 DCM patients and 14 healthy volunteers.After the Primers were designed,the target sequence of DCM patients and healthy volunteers was amplified by PCR.the second-generation sequencing method was used to measure the base sequences of all participants,then comparing them with the full-length sequence(NC＿000019.10)of CEACAM5 gene,and screening the SNP loci relating to DCM susceptibility.Finally Chi-square test was used to analyze the statistical differences of genotype frequency and allele frequency between the two groups.2.Collect the relevant clinical data of each subject,including: gender,age,height,weight,smoking history,drinking history,blood pressure,diabetes history,blood glucose,blood lipids,heart rate,BNP,NYHA classification of cardiac function,Left ventricular end-diastolic diameter Diameter(LVEDd),and Left atrial diameter(LAD),Long diameter of right ventricular,Left ventricular ejection fraction(LVEF),Pulmonary artery pressure(PAP),etc.The correlation between the polymorphism of CEACAM5 gene and the BNP,NYHA cardiac function classification and Cardiac ultrasound parameter of DCM patients was analyzed.Results:1.In this study,Three polymorphic loci of CEACAM5 gene that may be associated with DCM susceptibility were found: rs2072440327(3201G>T),rs782232638(3886G>T)and rs1232662004(20712G>T).2.The three polymorphic genotypes(GG/GT/TT)and alleles(G/T)at rs2072440327(3201G>T)of CEACAM5 gene were significantly different between DCM case group and normal control group.The distribution frequency of GG/GT/TT genotype at this site in DCM case group was 10.6%,85.1% and 4.3%,and the distribution frequency of G/T allele was 53.2% and 46.8%.The frequency of GT genotype and T allele in DCM group was significantly higher than that in control group,and the difference was statistically significant(P=0.001;P=0.002).The GT/TT genotype at this site may be the genetic susceptibility factor of DCM,individuals carrying GT/TT genotype at this site have a higher risk of disease,which is 32.48 times higher than individuals with GG genotype(OR = 32.48,95% CI=3.44-306.80,P=0.002).In DCM patients,there was no significant difference in the frequency distribution of three genotypes(GG/GT/TT)in BNP,NYHA cardiac function classification,LVEF,LVEDd,LAD,PAP and Long diameter of right ventricular(P>0.05).3.The three polymorphic genotypes(GG/GT/TT)and alleles(G/T)at rs782232638(3886G>T)of CEACAM5 gene were significantly different between DCM case group and normal control group.The distribution frequency of GG/GT/TT genotype at this site in DCM case group was 12.8%,80.9% and 6.4%,and the distribution frequency of G/T allele was 53.2% and 46.8%.The frequency of GT genotype and T allele in DCM group was significantly higher than that in control group,and the difference was statistically significant(P=0.001;P=0.001).The GT/TT genotype at this site may be the genetic susceptibility factor of DCM,individuals carrying GT/TT genotype at this site have a higher risk of disease,which is 26.44 times higher than individuals with GG genotype(OR = 26.44,95% CI=3.26-214.32,P=0.002).In addition,we also found that the LAD of the GT/TT genotype at this site was significantly higher than that of the GG genotype in DCM patients(mean ±standard deviation: 45.34 ± 8.53 vs GG 36.00 ± 6.07;P=0.013),and the Long diameter of right ventricular of the GT/TT genotype at this site was also significantly higher than that of the GG genotype(mean ± standard deviation: 80.44 ± 11.29 vs GG70.33 ± 5.68;P=0.038)(Table 16).There was no significant difference in NYHA cardiac function classification,LVEF,BNP,LVEDd and PAP.4.The three polymorphic genotypes(GG/GT/TT)and alleles(G/T)at rs1232662004(20712G>T)of CEACAM5 gene were significantly different between DCM case group and normal control group.The distribution frequency of GG/GT/TT genotype at this site in DCM case group was 40.4%,12.8% and 46.8%,and the distribution frequency of G/T allele was 46.8% and 53.2%.The frequency of TT genotype and T allele in DCM group was significantly higher than that in control group,and the difference was statistically significant(P=0.007;P=0.001).Using binary logistic regression to analyze the SNP and susceptibility to DCM at this site,no association was found between the polymorphism of this site and the incidence of DCM(P>0.05).In DCM patients,there was no significant difference in the frequency distribution of three genotypes(GG/GT/TT)in BNP,NYHA cardiac function classification,LVEF,LVEDd,LAD,PAP and Long diameter of right ventricular(P>0.05).Conclusions:1.The SNP of rs2072440327(3201G>T)and rs782232638(3886G>T)located in the intron region of CEACAM5 gene may be related to the genetic susceptibility of DCM,and the GT/TT genotype at these two sites may be one of the genetic susceptibility factors of DCM.2.The SNP at rs1232662004(20712G>T)in the exon of CEACAM5 gene may be related to the genetic susceptibility of DCM.3.The SNP at rs782232638(3886G>T)located in the intron region of CEACAM5 gene was associated with LAD and Long diameter of right ventricular in DCM patients.The mutation of this site can be used to predict the more serious expansion of the LAD and Long diameter of right ventricular in DCM patients.