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Correlation Between Growth Differentiation Factor-15(GDF-15) Gene Polymorphism Loci+157A/T And Unstable Angina Pectoris

Posted on:2015-02-02Degree:MasterType:Thesis
Country:ChinaCandidate:M L ZhaoFull Text:PDF
GTID:2284330431980598Subject:Oncology
Abstract/Summary:PDF Full Text Request
Objective:UAP(unstable angina pectoris) is an significant component of ACS(acutecoronary syndrome), is an acute cardiac event of coronary heart disease, isbetween chronic stable angina and acute myocardial infarction in the middleof the clinical syndrome. Include (1) Onset of angina pectoris2) worseningangina pectoris (3) resting angina (4) angina (5) variant angina after infarction;Unstable angina is a pathology of coronary plaque rupture in platelet adhesionand aggregation caused by bleeding in turn, is characterized by symptoms ofangina was progressively increased, if not treated promptly or timelyintervention also can progress to acute myocardial infarction; unstable anginacompared with stable angina, Significantly reduced activity tolerance, morepain,Longer duration of pain. Some patients after several months ofprogression to acute myocardial infarction;GDF-15(growth differentiation factor-15) has been named asmacrophage inhibitory factor l (NAG-1) non-steroidal anti-inflammatoryactivation of gene-1(MIC-1), previous studies indicated that GDF-15associated with tumor; recent study found that GDF-15is closely related toheart unstable angina, In the course of unstable angina its protective role.GDF-15high expression in the placenta and prostate tissue,not expressed inthe heart and other tissues, but in the event of ischemia or myocardialischemia/reperfusion injury, GDF-15expression was significantly increased.Previous studies showed that human GDF-15gene in dozens of SNPsites, mostly nonsense SNP, where located in exon3of the SNP: rs1059369,rs1059519, rs1058587(loci were+157A/T-3148C/G,+2438C/G) resultsin change the amino acid sequence of GDF-15precursor protein, which maychange the protein activity and stability of the GDF-15, we thereby to beginto explore the sites of GDF-15+157A/T of SNP: rs1059369polymorphismswith unstable angina relevant. 1.coronary angiography performed by comparing all subjects plasmalevels of GDF-15to analyze the relationship between GDF-15levels andunstable angina;2.using PCR-LDR method (enzyme link method) rs1059369genotypinganalysis of gene polymorphisms+157A/T of SNP: rs1059369partingbetween the two groups separately for each different phenotypes andphenotype comparison between the two groups, and thus to analyze GDF-15gene polymorphism sites+157A/T with unstable angina correlation.methods:1.Coronary angiography-positive,50cases in the control group40cases ofcoronary angiography overcast. Double antibody (ELlSA) method for thedetermination of serum levels of GDF15-sandwich enzyme in all patients, andanalyzed statistically.2.Using PCR-LDR for all patients SNP genotyping analysis. Designspecific primers upstream and downstream primers, multiplet PRCamplification SNP, to obtain the gene fragment containing the mutation in thegene fragment of the fluorescent probe is set, When the probescomplementarity gene of fragment of DNA matching, catalyzed by acid ligasethe ester bond connecting two adjacent probes to form a product, if there aretwo joints oligonucleotide probe base mismatch, The response will not be ablebe connected.Finally, sequencing instrument reads sequencedthen werestatistically analyzed.Results:1Coronary angiography is generally characterized by pulsating positivegroup and the control groupCoronary angiography between positive group with the control group,significant differences of age, gender, smoking, high blood pressure, bloodglucose and lipid levels were not. Coronary angiography-positive men thanwomen, and coronary artery by coronary angiography is normal, chest painsymptoms in the control group of women than men, in line with a highincidence of coronary heart disease and cardiac neurosis men women with a high incidence of epidemics Learning Features(Table1)2GDF-15levels were measured coronary angiography positive andnegative serum Experimental results:50cases of coronary-positive patientswith GDF-15levels:1610.08±312.80,40cases of coronary patients withnegative group GDF-15levels:630.73±132.57;3GDF-15gene polymorphisms+157A/Trs1059369polymorphismgenotyping for the [A/T]: AT, TT, AA, OO, product size50/A,54/T. Whichcoronary angiography positive component type: AT Type20TT type7AAtype19OO type4;coronary angiography negative component type: AT Type18TT type8AA Type13OO type1.4coronary angiography positive patients and coronary angiographynegative patients+157A/T rs1059369[A/T] polymorphism genotypingcompare two different phenotypes (P=0.57Table1) was No statisticalsignificance5coronary angiography positive patients and coronary angiographynegative patients+157A/T: Phenotypic analysis between each rs1059369[A/T] polymorphism genotyping groups (AT group P=0.63,TT group P=0.45, AA group P=0.59,00Group P=0.26. table2) no statisticallysignificant.Conclusion:1.Coronary angiography-positive peripheral blood plasma of GDF-15was significantly higher than plasma levels of coronary angiography negativegroup (P <0.01), coronary angiography was positive higher the serum levels ofGDF-15; coronary angiography negative low serum levels; the difference wasThe difference were statistically significant(Table2)2.GDF-15gene polymorphisms+157A/T: rs1059369polymorphismand unstable angina was no significant correlation: rs1059369polymorphismdid not affect the biological activity of GDF-15may not change the protein ofGDF-15activity and stability, rs1059369polymorphism can not directly orindirectly affect the expression of GDF-15levels in patients with unstableangina plasma, rs1059369polymorphism [A/T] distribution of coronary angiography and coronary angiography positive negative no significantdifferences were in the (positive group: AT Type20TT type7AA type19OOtype4;negative group:AT Type18TT type8AA Type13OO type1),rs1059369polymorphism sex with unstable angina not statistically significant.However, this research is the small sample size research, the results maynot be representative of the true clinical reality, we need to conduct furtherresearch for a long time a large sample. This study is an initial series of studiesexploring the hospital, pre-trial series of experiments, has taken a crucial firststep in a series of studies, be inspired to follow tips and more in-depthresearch, which for Unstable Angina angina study has important referencevalue for unstable angina pathogenesis, treatment, prognosis studies providenew ideas and research based。...
Keywords/Search Tags:Growth Differentiation Factor-15(GDF-15), unstable angina pectoris(UAP), Single nucleotide polymorphism(SNP), Loci, +157A/T, rs1059369
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