The Study Of Relationship Between Lymphotoxin-α And Acute Coronary Syndrome Pathogenesis

Objective:To investigate lymphotoxin-α(LTA) gene C804A and A252Gpolymorphism,LTA,tumor necrosis factor alpha (TNF-α),Myeloperoxidase (MPO)and intercellular adhesion molecule (ICAM-1) in acute coronary syndrome group andcontrol group.And,to analyze the relationship between LTA804,LTA252 site genesmutation with inflammation factor gene expression and the extent of coronary arterydisease.To disclose an inherit cause and inflammatory response related to thepathogenesis of ACS.Methods:We select 186 patients who were hospitalized in Tianjin first centralhospital cardiovascular department from Sep 2007 and Dec 2008.Their clinicinformation was recorded,such as gender,age,smoking,drinking,CHD familyhistory,diabetes history,triglyceride,total cholesterol,low-density lipoproteincholesterol,high density lipoprotein cholesterol,uric acid,fasting plasma glucose,etc.And,all patients were undergone with coronary angiography.Diagnosis of unstableangina pectoris(UAP) or acute myocardial infarction(AMI) was performed byaccording to ACC/AHA Guidelines.According to the results of coronary angiography,186 patients were divided into ACS group (106 cases) and control group (80 cases).ACS group was divided into UAP and AMI subgroup.Their serum levels of tumornecrosis factor-α,lymphotoxin-α,Myeloperoxidase and intercellar adhesion moleculewere measured by enzyme-linked immunosorbent assay (ELISA).DNA was extractedwith AxyPrep DNA reagent.The mutation of the LTA 804C→A,252A→G transitionwas examined by polymerase chain reaction and identified with agarose gelelectrophoresis.Using statistic software SPSS 13.0 to analyze the data,Chi square testwere used to compare numeration data between two groups.Measurement data wereexpressed as mean±SD,followed F analysis,t or q test was used to comparemeasurement data between groups.The level of significance was set at P＜0.05.Results:The level of TNF-α,MPO,LTA and ICAM-1 in ACS group weresignificantly higher than control group (P＜0.01).The level of TNF-αand ICAM-1 inacute myocardial infarction (AMI) group were higher than that in unstable anginapectoris (UAP) group.There were no differences of MPO and LTA between AMI group and UAP group.The serum level of TNF-αwas associated with the degree ofcoronary lesion in ACS group.The levels of TNF-αin two or three vessels coronarylesion group were significantly higher than that in one vessel coronary lesion group.There were no differences of MPO,LTA and ICAM-1 in ACS group with thedifferent coronary lesion.There were three kinds of genotypes,CC,AA and CA inLTA gene 804.LTA gene C804A genotype frequencies and distributions wereequilibrium in ACS group and control group.The levels of TNF-αwith differentgenotypes had no statistic difference in ACS group with the different coronary lesion.The plasma levels of TNF-αwith mutation genotypes were significantly differentboth in two vessels and three vessels coronary lesion of ACS group.The levels ofTNF-αin mutation genotypes (CA and AA) were higher than that in CC type.Therewere three kinds of genotypes AA,AG and GG in LTA gene 252.LTA gene A252Ggenotype frequencies and distributions were different in ACS group and control group.Genotype of AG are highest in ACS group.There were no differences of LTA geneA252G genotype frequencies and distributions in patients with different coronarylesions of ACS group.There were no differences of TNF-α,MPO,LTA and ICAM-1with different genotype of LTA gene C804A and A252G in ACS and control group.Conclusion:1,The levels of TNF-α,MPO,LTA and ICAM-1 in ACS group werehigher then that in control group.The levels of TNF-αand ICAM-1 in AMI groupwere higher than that in UAP group.TNF-αwere related with coronary lesionextension in ACS group.TNF-α,ICAM-1 may be the marker of plaque rupture,theyalso had influence on ACS development and prognosis.2,There were no differencesof LTA gene C804 genotype frequencies and distributions in ACS group and controlgroup.Interaction was not presented between LTA gene C804A mutation and ACS.3,The mutation of LTA gene A252G was associated with ACS.May be it was one of therisk factor of coronary heart disease.4,The more severity coronary lesion was inmutation LTA gene C804A,the more higher levels of TNF-αin ACS group.LTA geneC804A mutation may promote inflammation factors release.