The Association Of CXCL12/CXCR4 Gene Polymorphism With The Genetic Risk And Severity Of Coronary Stenosis In Patients With Coronary Artery Disease

Objective To investigate whether the gene polymorphisms of CXCL12 and CXCR4 are associated with the genetic risk and severity of coronary stenosis in patients with coronary artery disease(CAD)in Chinese Han population who lived in Lanzhou.Methods Kompetitive Allele Specific PCR(KASP)was performed to identify the genotypes of rs2297630,rs2322864,rs266085 and rs266087 polymorphisms for 302 CAD patients and 302age-and gender-matched healthy controls who had been recruited in Second hospital of Lanzhou university from November of 2017 to June of 2018.The severity of CAD patients were assessed by the Gensini scoring system according to the results of coronary arteriography.Utilizing the SHEsis online software and haploview software to analysize the Hardy-Weinberg Equilibrium,Linkage disequilibrium and build Haplotype.Moreover,the differences of genotype frequency and allele frequency between 2 groups were compared by X~2 analysis in SPSS19.0.And the association of rs2297630,rs2322864,rs266085 and rs266087 polymorphisms with genetic risk of CAD and Gensini scores were analyzed by unconditional logistic regression and multivariate linear regression respectively.Results (1)We found significant differences(P<0.05)in the genotype and allele frequencies of4 SNPs(rs2297630 G>A?rs2322864 T>C?rs266085C>T?rs266087 G>A)between the CAD group and healthy control through X~2 analysis.(2)Under three genetic models,logistic regression analysis reveals that except for the AG genotype in the codominant model,all other genetic models were significantly associated with increased risk of CAD,and the subjects with AA genotype had higher risk of CAD compared with those with GG genotype.After adjustment for the cofounders,rs2322864 remained associated with the increased risk of CAD and the subjects who carried the CT genotype had higher risk of CAD compared those with TT genotype.What's more,rs266085 and rs266087 on the CXCL12 gene acted as protective role in CAD.(3)The Kruskal-Wallis test found that there were statistically significant differences in rs2297630 after comparing the gensini score level of AA genotype with AG genotype and GG genotype respectively.Besides,there was no significant difference of Gensini score level between AG genotype and GG genotype.We also found significant differences of Gensini score level between AG genotype and GG genotype in rs266087.However,there were no siginificant difference in other SNPs in terms of Gensini score level in different genotypes.(4)Regression analysis showed that rs2297630 polymorphism was associated with Gensini scores level(P<0.05).People who carried the AA genotype suffered from more serious coronary stenosis compared with GG genotype carriers.Meanwhile,under the recessive model,compared with AG+GG,AA genotype was correlated with more serious coronary stenosis as well(P<0.05).The association remained significant after adjustment for confounding factors(P<0.05).There were no association between other SNPs and the Gensini score level.(P<0.05).(5)The results of Linkage disequilibrium analysis showed that rs266087 and rs266085 can build a significant haplotype(D'=0.745,r2=0.529,P<0.05).However,no significant haplotype were found when taking rs2297630 iinto consideration.Moreover,haplotype analysis showed that the haplotype GT,GC and AC of rs266087 andrs266085 had significant differences between case and control groups,the haplotype AC and GT were correlated with lower risk of CAD.On the contrary,the GC haplotype was associated with higher risk of CAD(P<0.05).Conclusion (1)Our study indicated that the gene polymorphism of CXCL12 rs2297630rs266085 and rs266087 were associated with the genetic risk of CAD.SNP rs2297630 was associated with the severity of coronary stenosis and the patients who carried the AA genotype suffered from more serious coronary stenosis.Moreover,there is no correlation between the SNP rs266085,rs266087 and the severity of coronary stenosis.(2)The gene polymorphism of CXCR4rs2322864 was associated with genetic risk of CAD,however,not with the severity of coronary stenosis.(3)The haplotypes of rs266087 and rs266085 were associated with the genetic risk of CAD.