Association Of ERBB3,TENC1,ACVR1B,DGKA Genetic Polymorphisms With Pathogenesis And PCI Prognosis Of Coronary Artery Disease

Objective:Using gene chip technology screening differentially expressed genes in aorta,internal mammary artery tissue to find a new target gene that associated with coronary heart disease in patients with coronary heart disease in Xinjiang;Discuss correlation and risk factors of ERBB3,TENC1,ACVR1B,DGKA genes tag SNP polymorphism with coronary heart disease in Xinjiang Uygur and Han;Discuss relationship between genotypes of ERBB3,TENC1 gene tag SNP polymorphism and prognosis of coronary heart disease in post-PCI patients.Methods:1)To obtain gene expression data of the aortic lesions（lesions）and the internal mammary artery tissue（control）were Using Affymetrix Human U133 Plus 2.0 cDNA microarray,Mainly through photolithographic in situ synthesis of oligonucleotides patented technology.DNA microarray data was subjected to differential gene expression analysis,cluster analysis,signal interpretation and gene annotation data processing by means of biological information databases,software and websites.we tried to screen out the Differentially expressed genes in an attempt to identify some of the genes that Differentially expressed and might be associated with atherosclerosis and coronary heart disease;2)By A casecontrol study,we selected 645 cases diagnosed CAD by coronary angiography and healthy sex,age,ethnicity-matched control group of 720 cases.Using Taqman genotyping technology and methods genotyped tag SNP of ERBB3,TENC1,ACVR1B,DGKA gene,analyzed relations of tag SNPs and coronary heart disease;3)followed up PCI post operation coronary heart disease patients in Xinjiang for ERBB3,TENC1 gene loci tag SNP genotyping,analyzed the relationship between the tag SNPs different genotypes and coronary heart disease adverse events after PCI.Results:1)chips Result obtained total of 1275 differentially expressed genes,among them 462 genes were up-regulated,and 813 down-regulated genes.GO biological function analysis shows that,14 genes involved in angiogenesis,6 genes involved in differentiation of endothelial cells,16 genes involved in cell proliferation of vascular smooth muscle cells,15 genes involved in the proliferation of endothelial cells,11 genes involved in the platelet activity,22 genes involved in calcium-mediated signaling pathways,13 genes involved in the regulation of PI3K signaling pathway,18 genes related to endothelial development functions,29 genes involved in negative regulation of cell motility,and 24 genes related to extracellular matrix structure composed;2)ERBB3 gene rs877636,TENC1 gene rs11170388 and rs 12816417 genotypes of polymorphic loci have differences in the distribution between coronary heart disease group and control group of Han population in Xinjiang.There are obvious differences in allele,genotype distribution of DGKA gene rs2291615 locus and TENC1 gene rs 10747658,rs10437946 locus between coronary heart disease and a control group of Uyghur.dominance model,additive mode of both ERBB3 gene rs877636,and TENC1 gene rs11170388,rs12816417 locus show significantly association with coronary heart disease In the Han population.Dominant and recessive models of DGKA gene rs2291615 locus,recessive model of TENC1 gene rs10747658 locus,dominant and the additive model of rs 1043 7946 locus have differences in frequency distribution between coronary heart disease group and control group of Uyghur,and Display association with coronary heart disease;3)By 2 years follow-up found no correlation between ERBB3 gene rs877636 polymorphism and poor prognosis of PCI after coronary heart disease.The results of TENC1 gene rs12816417 polymorphism loci different genotypes and postoperative adverse events Relevance show that,in patients with postoperative stent restenosis CC genotype was significantly higher than CT/TT type carriers,and the total incidence of MACE having a significant difference between different genotype,suggesting that rs 12816417 polymorphism may be a risk factor for adverse events occurring after PCI in patients with coronary heart disease.Conclusion:1)by gene chip technology discovered four new genes associated with coronary heart disease,TENC1,ERBB3,DGKA,ACVR1B genes are differentially expressed in atherosclerotic aorta and the internal mammary artery（control）tissue;2)ERBB3 gene rs877636 locus,TENC1 gene rs 12816417 polymorphism associate with occurrence of coronary heart disease in Han population in Xinjiang;3)There is no correlation between ERBB3 gene rs877636 polymorphism and adverse events of coronary artery disease after PCI.But TENC1 gene rs 12816417 polymorphism and occurrence of MACE adverse events in patients with coronary artery disease after PCI has association.