Correlation Research Between ALDH2 Polymorphisms And Acute Myocardial Infarction Including The Inflammation Levels Of The Early Phase In Chinese Han People

BackgroundAcute myocardial infarction(AMI) is caused by atherosclerotic coronary artery plaque erosion or rupture which lead to transient,partial or complete arterial occlusion.More and more evidences support the concept that inflammation plays an important role in the initiation and progression of myocardial infarction.As an acute-phase reactant marker for underlying systemic inflammation,hs-CRP has been reported to be elevated in patients with AMI.CD40L is known to be an inflammation mediator of athrosclerosis involved in atherosclerotic lesions and plaque stability,and is likely to trigger cells trapped in the thrombus.Aldehyde dehydrogenase 2(ALDH2) is one of the key enzymes of alcohol metabolism which could catalyzes acetaldehyde to acetic acid in vivo.ALDH2 is encoded by the ALDH2 gene on chromosome 12 and located in the mitochondria by which it was also called mitochondria ALDH.There is a missense point mutation(G to A) in exon 12 of all the 13 exons in the gene fragments,which leads to the replacement of the 487th amino acid residue Glu with Lys in ALDH2 peptide sequence.There are three ALDH2 genotypes(ALDH2~*1/~*1,ALDH2~*1/~*2, ALDH2~*2/~*2) in the population.Many researchers indicated that actived ALDH2 could reduce the ischemic damage to the heart and mutant ALDH2(ALDH2~*1/~*2, ALDH2~*2/~*2) is a risk factor of AMI.And our recent research suggest that mutant ALDH2 had an association with AMI.However,the relationship between ALDH2 polymorphisms and inflammation levels in the early phase of AMI has not been studied.We were aim to investigate whether ALDH2 polymorphisms could influnce the levels of serum hs-CRP and sCD40L in the early phase of AMI. Objectives1.To investigate the correlation between aldehyde dehydrogenase 2(ALDH2) polymorphisms and acute myocardial infarction(AMI) in Chinese Han people.2.To evaluate the role which ALDH2 polymorphisms had played in the early stage of AMI that can influence the inflammation levels and the possible mechanisms initially.MethodsA case-control study method was adopted.106 acute myocardial infarction patients who came to Qilu Hospital of Shandong University from March 2008 to January 2009 and 212 cases with no coronary heart disease,who were chosen according to the constituent ratio by age and gender of the patients group,were involved in this study to analysis the influence of the ALDH2 polymorphisms to the incidence and the inflammation levels in the early stage of AMI.The clinical base-line data were collected using a structured questionnaire containing the subjects' clinical characteristics,including age,gender,body mass index(BMI),smoking,drinking, hypertension,diabetes,lipid items,family history of coronary heart disease(CHD),et al.The lipid items included totle chelesterol(TC),triglyceride(TG),low-density lipoprotein chelesterol(LDL-C),high-density lipoprotein chelesterol(HDL-C).Blood samples were collected at the ulnar vein of 2 ml in tubes within 12 hrs after AMI incidence.We extrated the DNA with a DNA extration kit,then took the polymerase chain reaction(PCR) to extend DNA production.After purifying the DNA production, we definited the ALDH2 genotypes by the method of gene sequnecing of the Biosune Corporation.Patients were divided into two subgroups according to their ALDH2 genotypes:wild genotype(ALDH2~*1/~*1,n=52) and mutant genotypes(ALDH2~*1/~*2, ALDH2~*2/~*2,n=54).We determine the hs-CRP and sCD40L concentration by nephelometry and ELISA technique respectively.Statistical analysis were performed using SAS software version 9.1.Comparison between two groups of the ALDH2 polymorphisms and the concentration of hs-CRP and sCD40L of the two subgroups was performed using the chi-square test,unpaired t-test or non-parametric means test for continuous variables.After adjustment for confounding factors,a multivariate logistical regression analysis was performed to identify the odds radio and 95%CI.A P-value of less than 0.05 was considered statistically significant.Results1.The difference of the constituent ratio of age and gender,body mass index(BMI), smoking history of the two group was not significant.The mutant ALDH2 genotype,hypertension,diabetes,TC,LDL-C and the concentration of hs-CRP and sCD40L of the AMI group were more or higher than that in the control group (P＜0.05).However,the concentration of HDL-C of the AMI group were lower than that in the control group(P＜0.05).2.After adjustment for BMI,hypertension,diabetes,smoking,TC,TG,HDL-C, LDL-C,a multi-variable logistic regression showed the mutant genotype (ALDH2*~1/~*2,ALDH2~*2/~*2) was an independent risk factor of the incidence of AMI(OR=1.972,95%CI=1.048～3.710).After inclusion of drinking,the odds ratio was 2.003(95%CI=1.060～3.785).3.The concentration of hs-CRP and sCD40L of AMI group were higher than the control group(P＜0.05).Both the hs-CPR and the sCD40L of mutant genotype subgroup were rather higher than that of the wild-type genotype(ALDH2~*1/~*1) subgroup(P＜0.05).Conclusions1.ALDH2 polymorphisms was an independent risk factor of acute myocardial infarction(AMI) in Chinese Han people.2.The mutant genotype of ALDH2(ALDH2~*1/~*2,ALDH2~*2/~*2) was associated with the higher inflammation levels in the early phase of AMI.3.ALDH2 genotypes which acted on the incidence of AMI might not only by the alcohol consumption,but also by regulating the inflammation condition at the molectular level probably.