Correlation Between The Gene Polymorphism Of Lipoprotein-associated Phospholipase A₂ And Acute Coronary Syndrome

Objective:To explore the correlation between Lp-PLA₂and ACS,and analyze the clinical value in the genetic susceptibility,risk level and prognosis of ACS.Methods:We selected 92 inpatients who underwent coronary angiography in the Department of Cardiology in Kunshan First People’s Hospital from June 2019 to October 2020.And they are divided into three groups according to the results of the angiography,including the ST-segment elevation acute myocardial infarction group（39 cases）,non-ST-segment elevation acute myocardial infarction group（15 cases）,unstable angina group（38 cases）.25 inpatients who have the negative angiography were selected as the control group.Then,we collected age,gender,anamnesis,blood lipids,hs-CRP,Lp-PLA₂,etc.of the 117 inpatients.We also sequenced the two gene polymorphisms of Lp-PLA₂gene A379V and T403C with the Gene Sequencer,calculated GRACE score and Gensini score,and performed statistical analysis.Results:1.There was no statistical difference among gender,Lp-PLA₂level,blood lipids,diabetes,smoking,drinking and other groups in each group（P>0.05）.The age and GRACE score in STEMI group were lower than those in the other groups（P<0.05）,and the level of high-sensitivity C-reactive protein in the control group was lower than in the other groups（P<0.05）.2.The preoperative Lp-PLA₂was 167.71±60.06ng/m L,and the postoperative Lp-PLA₂was168.73±61.12ng/m L,before being divided into two groups according to whether PPCI was performed.Paired sample T test P=0.824,95%CI:（-10.094-8.064）.The difference before and after PPCI was-4.5±35.65ng/m L in the PPCI group,and the difference was 1.55±38.11ng/m L in the group without PPCI during the operation,t=0.655,95%CI:（-24.509-12.404）,P=0.515（>0.05）.Intra-group comparison,before and after PPCI was not performed,t=-0.258,P=0.797,95%CI:（-39.44-30.44）;PPCI group was compared before and after operation,t=0.117,p=0.907,95%CI:（-24.85-27.96）.Preoperative and postoperative Lp-PLA₂can not be considered different regardless of whether PPCI treatment is performed.3.The P value between Lp-PLA₂and hs-CRP is 0.4959.The P value between Lp-PLA₂and the degree of coronary artery disease（Gensini score）is 0.6670.And the P value between Lp-PLA₂and the prognosis of acute coronary syndrome（GRACE score）is 0.3517（Pearson test）.We cannot consider a linear relationship between Lp-PLA₂and the three indicators.4.T403C and A379V genotypes are tested by Hardy-Weinberg equilibrium law,they are in line with the genetic equilibrium law and can represent the population（P>0.05）.5.In the UA group,the average value of Lp-PLA₂a was different between the ⁴⁰³A⁴⁰³A and⁴⁰³A⁴⁰³G+⁴⁰³G⁴⁰³G genotypes（P=0.023）,and the prevalence of hypertension in the ⁴⁰³A⁴⁰³A genotype was significantly lower than that of the ⁴⁰³A⁴⁰³G+⁴⁰³G⁴⁰³G genotype（P=0.003）.Also in the UA group,the rate of drinking and diabetes mellitus in ³⁷⁹A³⁷⁹A genotype was significantly lower than in ³⁷⁹A³⁷⁹G+³⁷⁹G³⁷⁹G genotype group（both P<0.001）.In STEMI,NSTEMI and the control group,no difference was found between the ⁴⁰³A⁴⁰³A genotype and ⁴⁰³A⁴⁰³G+⁴⁰³G⁴⁰³G genotype（P>0.05）.6.Four subjects had coronary stent restenosis,and their genotypes（T403C+A379V）were⁴⁰³A⁴⁰³G+³⁷⁹G³⁷⁹G,⁴⁰³A⁴⁰³A+³⁷⁹G³⁷⁹G,⁴⁰³G⁴⁰³G+³⁷⁹G³⁷⁹G,⁴⁰³A⁴⁰³A+³⁷⁹G³⁷⁹G respectively.Among them,the only genotype of the patient admitted to the hospital again due to acute ST-segment elevation myocardial infarction was ⁴⁰³G⁴⁰³G+³⁷⁹G³⁷⁹G.7.After logistic stepwise regression analysis,the independent risk factors for the onset of ACS are age,gender,and hypertension（P<0.05）.Gender and high-sensitivity C-reactive protein are risk factors for the severity of coronary artery disease（P<0.05）.Age is a risk factor for the prognosis of ACS（P<0.05）.The T403C and A379V gene polymorphisms could not be found to be statistically related to the risk,the severity and the prognosis of ACS（P>0.05）.8.The linkage analysis of T403C and A379V showed that D’=0.994,r2=0.028,showing strong linkage disequilibrium.9.The distribution of the 403A379G haplotype in the NSTEMI group and the control group was statistically different（P<0.05）,that is,the risk of non-ST-segment elevation myocardial infarction carrying both the ⁴⁰³A and ³⁷⁹G alleles（OR=0.361,95%CI:0.137～0.951）.The remaining haplotypes of T403C and A379V were not significantly different between ACS and the control group.Conclusion:1.The level of Lp-PLA₂was not found to be statistically different before and after coronary angiography.2.There is no linear correlation between Lp-PLA₂and hs-CRP.There is no linear correlation between Lp-PLA₂and the degree of coronary artery disease.There is no linear correlation between Lp-PLA₂and the prognosis of acute coronary syndrome.3.T403C and A379V genotypes and allele G have no significant correlation with the onset risk,the severity and the prognosis of ACS（P>0.05）.4.The Lp-PLA₂level in⁴⁰³A⁴⁰³A genotype was higher than⁴⁰³A⁴⁰³G+⁴⁰³G⁴⁰³G genotype.There was no statistical difference in Lp-PLA₂levels between g⁴⁰³G⁴⁰³G genotype and⁴⁰³A⁴⁰³A+⁴⁰³A⁴⁰³G genotype,³⁷⁹A³⁷⁹A genotype and³⁷⁹A³⁷⁹G+³⁷⁹G³⁷⁹G genotype and³⁷⁹G³⁷⁹G genotype and ³⁷⁹A³⁷⁹A+³⁷⁹A³⁷⁹G.5.The value of Lp（a）in UA group was different between the⁴⁰³A⁴⁰³A and⁴⁰³A⁴⁰³G+⁴⁰³G⁴⁰³G genotypes.The prevalence rate of hypertension in the ⁴⁰³A⁴⁰³A genotype was significantly lower than in the ⁴⁰³A⁴⁰³G+⁴⁰³G⁴⁰³G genotype;drinking rate and the prevalence rate of diabetes in the³⁷⁹A³⁷⁹A genotype were significantly lower than in the ³⁷⁹A³⁷⁹G+³⁷⁹G³⁷⁹G genotype group.6.The onset risk of non-ST segment elevation myocardial infarction carrying both the ⁴⁰³A allele and the ³⁷⁹G allele at the same time increased.