Expression Of Lncrna Anril In Peripheral Blood Of Patients With Coronary Heart Disease And Its Clinical Significance

Background:Coronary atherosclerotic heart disease,or coronary heart disease for short,is a chronic,multi-factorial inflammatory disease that can lead to acute coronary syndrome and sudden cardiac death.Stroke diseases such as myocardial infarction caused by coronary heart disease are still the main causes of death and disability in the global population.The incidence of the disease increases with the age of the patients,and the initial onset of the disease tends to become younger.Although cardiovascular interventional therapy is developing rapidly at present,there are still a large proportion of patients with coronary heart disease who cannot be diagnosed accurately at the early stage and cannot be treated effectively when myocardial infarction attacks.Acute coronary syndrome and other serious stages of coronary heart disease will cause serious damage to myocardial cells and eventually lead to myocardial cell necrosis,apoptosis,hypertrophy or fibrosis.The study found that coronary heart disease is related to family history.At the same time,there are many clear risk factors,such as diabetes,hypertension,hyper-lipidemia,smoking and so on.This means that the occurrence and development of coronary heart disease are closely related to the genetic basis.Genome-wide association study（GWAS）found that gene variation in chromosome 9p21 gene region is one of the risk factors for cardiovascular diseases.Chromosome 9p21 is the most successfμl genetic factor in the study of human coronary heart disease and other forms of cardiovascular and cerebro-vascular diseases such as stroke,peripheral arterial diseases and aneurysms.Although much progress has been made in recent years,the mechanism of its role in the occurrence and development of atherosclerosis is not completely clear.The 9p21segment contains many SNP loci that may be related to coronary heart disease,but these SNP loci are almost all located in the non-coding region.the protein coding gene closest to the region related to this coronary heart disease is the ink4b-ARF-ink4a locus separated from it by several thousand base pairs（kb）The ink4b-ARF-ink4a locus is about 35kb long and contains three known coding genes:CDKN2B（INK4b）and CDKN2A（including INK4a and ARF）,which encode two cyclin-dependent kinase inhibitors p15^INK4b,p16^INK4a,and another protein p14^ARF,all of which participate in cell cycle regulation.However,the core segment of the SNP locus at chromosome 9p21CAD risk overlaps with the exon13-19 segment of the lncRNA-ink4 locus antisense strand non-coding RNA in the ink4 locus（ANRIL）on the ink4 locus antisense strand.ANRIL is expressed in a variety of tissues and cell types affected by athero-sclerosis,and ANRIL contains a variety of linear and cyclic isomers.However,it is not clear why these transcription products are involved in the pathogenesis of arteriosclerosis.Here,we boldly assume that the single nucleotide polymorphism（SNP）of the 9p21 locus will affect the expression of relevant region transcripts（such as ANRIL,CDKN2A/2B）,thus participating in the formation of atherosclerosis。Methods:231 coronary heart disease patients were selected as coronary heart disease group from 2016.02 to 2018.02 in our hospital department of Cardiology.In addition,447 healthy volunteers were included as the control group.The peripheral blood of two groups of patients was extracted.The relative expression of 3 single nucleotides in the region of 9p21:rs1333049,rs564398,rs2811712,and lncRNA-ANRIL,CDKN2A,CDKN2B were measured by RT-PCR method.The correlation of each variable was analyzed,and the sensitivity and specificity of the expression of ANRIL in the diagnosis of coronary heart disease were analyzed.Results:The SNPs rs1333049 allele G of the coronary heart disease group was significantly lower than that of the control group（P<0.05）,and the rs1333049 allele G was positively correlated with the expression of ANRIL（exon1-2）and ANRIL（exon17-18）（r=0.3402/0.3124,all P<0.05）,and the expression of the relative value of ANRIL（exon1-2）and ANRIL（exon17-18）in coronary heart disease group was significantly lower than that of the control group（P<0.01）,and the ROC curve showed that ANRIL（exon1-2）and ANRIL（exon17-18）were statistically significant in the diagnosis of coronary heart disease（P<0.01）;The expression of lncRNA-ANRIL（exon1-2）was positively correlated with the expression of CDKN2A and CDKN2B（P<0.05）.LncRNA-ANRIL（exon17-18）was positively correlated with the expression of CDKN2A（P<0.0001）.Conclusion:ANRIL may affect the development of coronary heart disease by regulating the expression of CDKN2A/B.The expression of ANRIL may be influenced by the expression of SNPs rs1333049 of the chromosome 9p21 region.The expression of ANRIL in peripheral blood can be used as a specific marker for early diagnosis of coronary heart disease.