Font Size: a A A

Association Of The Platelet ADP Receptor P2Y12 And Coaglation Factor XIII-A Polymorphism With Coronary Artery Disease

Posted on:2011-10-05Degree:DoctorType:Dissertation
Country:ChinaCandidate:G D JinFull Text:PDF
GTID:1114360302983958Subject:Clinical Medicine
Abstract/Summary:PDF Full Text Request
PartⅠCoagulation FactorⅩⅢ-A Val34Leu Polymorphism and the Risk of Coronary Artery Disease and Myocardial Infarction in A Chinese Han PopulationBackgroundThere are controversial data regarding the impact of coagulation factorⅩⅢ-A subunit(FⅩⅢ-A) Val34Leu polymorphism in the pathogeneric of coronary artery disease(CAD) and myocardial infarction(MI).Assuming this genetic factor is associated with the thrombotic process,we explored the role of FⅩⅢ-A Val34Leu in CAD and MI in a Chinese Han population.Methods and ResultsWe recruited 195 consecutive CAD patients confirmed by coronary angiography as well as a group of 203 controls.FⅩⅢ-A Val34Leu polymorphism was determined through polymerase chain reaction-single strand conformational polymorphism analysis.We did not find the Leu/Leu genotype in CAD patients or controls.No significant difference in Val34Leu gene polymorphism distribution was found between CAD patients and controls(P=0.923).Subgroup analysis according to history of MI showed the heterozygote Val/Leu genotype was associated with a significantly decreased risk of MI(P=0.005;adjusted odds ratio=1.75;95%confidence interval =1.28-2.25).Furthermore,our study displayed that the frequency of the Leu34 allele in a Chinese Han population was lower than that in Caucasian populations(2.5 vs. 20.4-28.3%).ConclusionOur preliminary data indicates that the FⅩⅢ-A Leu34 allele may contribute a protective effect against the development of MI.There is a low prevalence of the Leu34 allele in Han Chinese compared to Caucasians. PARTⅡThe Association of ADP P2Y12 H1/H2 Polymorphism and Coronary Artery DiseaseBackgroundPlatelets play a key role in the pathophysiology of thrombosis after plaque rupture. Plaque rupture occurs spontaneously in patients with acute coronary syndromes(ACS), or may be induced in patients undergoing percutaneous coronary interventions(PCI).Among the multiple mediators of platelet activation,adenosine diphosphate(ADP) plays a pivotal role.Adenosine diphosphate binds to several receptors on the platelet membrane.Adenosine diphosphate is one of the most important mediators of both physiological hemostasis and thrombosis.After platelet activation,ADP is not only released from its intracellular storage granules but also further activates platelets, amplifying this process.There are 2 main purinergic receptor types in the membrane:the guanosine triphosphate(GTP)-coupled protein receptors,known as G-protein binding sites,and the ligand-gated ion channel.The latter receptor is designated P2X1 and the former is designated as P2Y,and each play a specific and complimentary role in platelet activation and aggregation.Recently,polymorphisms of the P2Y12 receptor have been associated with different degrees of platelet aggregation in healthy volunteers and also have been indicated to relate to artery disease.We investigate the P2Y12 receptor H1H2 gene polymorphism's frequency distribution and the association with coronary artery disease. Methods and ResultsTo observe the frequencies of the polymorphism of Adenosine Diphosphate(ADP) Receptor P2Y12 H1/H2 Haplotype in Chinese and the relationship between the polymorphism and coronary artery disease(CAD).ADP receptor P2Y12 H1/H2 Haplotype polymorphism was performed in 654 patients who were performed selective coronary angiography by using PCR-RFLP methods.The patients were classfied as 302 CAD patients group and 352 controls group.It was observed the relationship between the polymorphism of ADP receptor P2Y12 H1/H2 Haplotype polymorphism.The frequencies of genotype were H1/H1 78.6%,H1/H2 19.7%,H2/H2 1.7%.The frequencies of allele was H1 88.5%,H2 11.5%.The genotype distribution was in accordance with Hardy- Weinberg equilibrilum.A significant increase was found for the ADP receptor P2Y12 H1/H2 in CAD patients compared with controls(26.2%vs17.3%,χ2=8.808,P<0.05)。A significant increase was found for ADP receptor P2Y12 H1/H2 Haplotype H2 allele in CAD patients compared with controls(14.4%vs9.0%,χ2=8.987,P<0.01).Only the relationship of the APTT and the genotype were observed in this study.ConclusionThe polymorphism of ADP receptor P2Y12 H1/H2 Haplotype is present in Chinese and the H2 allele is a major risk factor for CAD patients.
Keywords/Search Tags:coronary artery disease, myocardial infarction, coagulation factor, polymorphism, gene, angiography, Chinese, Caucasian, Coronary Artery Disease, Platelet, Adenosine Diphosphate Receptor, P2Y12gene, Polymorphism, Restriction Fragment Length
PDF Full Text Request
Related items