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Association Of Aldehyde Dehydrogenase 2 Gene Polymorphism And Ischemic Preconditioning In Chinese Northern Han Patients With Acute Myocardial Infarction

Posted on:2011-12-11Degree:MasterType:Thesis
Country:ChinaCandidate:X X HaoFull Text:PDF
GTID:2154330332979845Subject:Internal Medicine
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BackgroundAcute myocardial infarction (AMI) is caused by atheroselerotic coronary artery plaque erosion or rupture which lead to transient, partial or complete arterial occlusion. Ischemic preconditioning (IP) is caused by repeated transient ischemic cardio-protection, which can reduce infarction size. And adenosine ethanol and PKC agonist can mimic IP.Aldehyde dehydrogenase 2 (ALDH2) is one of the key enzymes of alcohol metabolism which could catalyze acetaldehyde to acetic acid in vivo. ALDH2 is encoded by the ALDH2 gene on chromosome 12 and located in the mitochondria by which it is 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 isehemic damage to the heart and mutant ALDH2 (ALDH2 *1/*2, ALDH2*2/*2) is a factor of AMI. Chen et al found that the activity of ALDH2 was related with IP in animal model. But the relationship between ALDH2 genotypes in the human and IP is not yet clear. It is important to classify this point for the prevetion and treatment of acute myocardial infraction.The study aimed to investigate clinical coronary heart disease patients,the level of serum adiponectin and carotid atherosclerosis and endothelium dysfunction between metabolic syndrome combined and nonmetabolic syndrome.To study further the diagnostic value in atherosclerosis for metabolic syndrome,and identify the high risk patients.ObjeetivesTo investigate the correlation between aldehyde dehydrogenase 2 (ALDH2) polymorphisms and ischemic preconditioning (IP) in Chinese Northern Han people.MethodsA case-control study method was adopted. The study subjects were 83 acute myocardial infarction patients who came to Qilu Hospital of Shandong University from December 2005 to September 2006, including ischemic preconditioning 50 cases.Take 2ml arterial blood with sodium citrate anticoagulation. DNA was extracted from the blood. Design specific primers for the target DNA fragment, then go on PCR. Electrophoresis amplified products in the 2% agarose gel, divide the subjects into the wild-type group and the mutant group according to electrophoresis results. Inquire and collect the subjects'detailed information about the disease:age, sex, hypertension, type 2 diabetes mellitus, family history of cardiovaseular disease, face-reaction after drinking, smoking, history of alcohol, and other basic information. Take early morning blood (fasting for 10 hours), then measure fasting glucose, glycosylated hemoglobin Alc (HbAlc), total cholesterol (TC), triglyeerides (TG), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C); account the alcohol volumn through inquisition.SPSS 13.0 statistieal soft ware package was used for data analysis, x±s for numerical variables and frequency for classification variables. T-test was used in comparison of numerical variables andχ2 in classification variables. Multi-factor logistic regression was used to correlate age, hypertension, TG, smoking, family history of cardiovaseular disease and other factors with the relationship between ALDH2 genotypes in AMI patients and the IP prevalence. That P<0.05 showed a statistical significance. ResultsThe prevalence of IP was significantly higher in the ALDH2 GG genotype group than the AA/GA genotype group (P<0.01), but other basic clinical characteristics were similar between the two groups. After adjustment for age, sex, smoking, diabetes mellitus and infarction spot via a multivariable logistic regression, the GG genotype was an independent effect factor for IP (OR=3.32, P<0.01). However, inclusion of alcohol consumption as one of the independent variables downplayed the importance of the ALDH2 genotype (OR=3.13, P=0.03), and inclusion of hypertension and alcohol consumption further downplayed the importance of the ALDH2 genotype (P=0.23).Conclusion1. The ALDH2 GG genotype may be an independent effect factor for IP.2. The ALDH2 GG genotype might change IP incidence due to its influence on vessel vasodilation.
Keywords/Search Tags:Ischemic preconditioning, Gene Polymorphism, Single nucleotide, Acute myocardial infarction, Aldehyde dehydrogenase 2
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