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The Gene Polymorphisms Of SDF-13'A, MCP-1-2518G/A, CCR2-64I And CCR5△32 And Its Significance In Evaluating The Progonosis Of Patients With Dilated Cardiomyopathy

Posted on:2011-06-01Degree:MasterType:Thesis
Country:ChinaCandidate:Y Y LiFull Text:PDF
GTID:2154330332958790Subject:Clinical Laboratory Science
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Background and ObjectiveDilated Cardiomyopathy (DCM) is a typd of myocardial diseases characterized by the dilatation and reduction of the left ventricular function or of two ventricles. DCM is caused by a variety of diseases, among which autoimmune mechanism plays an important role in the pathogenesis of DCM. Chemokines are a kind of immune molecules which has variable biological functions to the different immune cells. Based on the amount and arrangement of the amino trmino cysteine residues, the chemokine superfamily can be divided into four subfamilies, namely as CXC, CC, C and CX3C. Chemokines and their receptors play an important role in physiological and pathological effect in the body through a variety of signaling ways. It is found that chemokines and their receptors SDF-1 3'A, MCP-1-2518G/A, CCR2-64I and CCR5â–³32 gene polymorphisms are closely related with many kinds of diseases (such as HIV-1, chronic inflammation, allergic diseases, transplant rejection, autoimmune diseases, some cancers). However, no reports were found about the role of SDF-1 3'A, MCP-1-2518G/A, CCR2-64I and CCR5â–³32 gene polymorphisms in the pathogenesis of DCM. Therefore, in this study the research objects were divided into two groups (the DCM group and the normal control group). The mutation frequencies of SDF-1 3'A, MCP-1-2518G/A, CCR2-64I and CCR5â–³32 were analyzed, and the relations between these mutation frequencies and left ventricular ejection fraction(LVEF), the grading of cardiac function, cardiac arrhythmia and viral myocarditis(VMC) medical history were studied to investigate the significance of SDF-1 3'A, MCP-1-2518G/A, CCR2-64I and CCR5â–³32 in evaluating the prognosis of patients with DCM.MethodsThe gene polymorphisms of SDF-1 3'A, MCP-1-2518G/A, CCR2-64I and CCR5â–³32 were detected by using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and PCR methods. The LVEF values of DCM patients were examined by using cardiac color ultrasound. The heart function was classified according to New York. Heart Association class (NYHA) criteria. Whether DCM patients were companied with arrhythmia is checked by ECG results.Results1. The SDF-1 3'A mutation frequencies of the DCM group and the normal control group were respectively 24.36% and 19.38%, and the difference has no significance (P>0.05). The MCP-1-2518G/G genotype was no significant difference (P>0.05). The CCR2-64I mutation frequencies frequencies respectively 22.44% and 23.75%, and there was no significant difference (P>0.05).2. The DCM patients were divided into the LVEF>35% group and the LVEF<35% group based on the LVEF values. Their SDF-1 3'A mutation frequencies respectively were 24.36% and 19.38%, and there was a significant difference (P<0.05). The MCP-1-2518G/G genotype frequencies was no significant difference (P>0.05). The CCR2-64I mutation frequencies respectively were 30.00% and 16.28%, so there was a significant difference (P<0.05).3. The DCM patients were divided into cardiac functionâ… -â…¢level group and cardiac functionâ…£level group based on NYHA standard. The SDF-1 3'A mutation frequencies were 33.33% and 15.38% respectively, so there was a significant difference (P<0.05); The MCP-1-2518G/G genotype frequencies was no significant difference (P>0.05); The CCR2-64I mutation frequencies were 29.49% and 18.53% respectively, so there was a significant difference (P<0.05).4. The DCM patients were divided into the normal cardiac rhythm group and the arrhythmia group based on whether had arrhythmia. Within the two groups, the distribution difference among SDF-1 3'A mutation frequencies, MCP-1-2518G/G genotype frequencies had no significance (P>0.05); The CCR2-64I mutation frequencies were 30.21% and 10.00% respectively. They had prominent difference (P<0.05).5. The DCM patients were divided into the non-VMC medical history group and the VMC medical history group, based on whether had VMC medical history. The SDF-1 3'A mutation frequencies had no significant difference within the two groups (P>0.05). The three genotype frequencies (AA, AG and GG) of MCP-1-2518G/A were respectively 24.49%,64.58% and 14.58% within the non-VMC medical history group, while they were 16.66%,36.67% and 46.67% within the VMC medical history group, with a significant difference (P<0.05). The CCR2-64I mutation frequencies were 28.12% and 13.33% respectively within the two groups, with a prominent difference (P<0.05).6. There was no CCR5â–³32 mutation among DCM patients and healthy people.Conclusions1. The SDF-1 3'A mutation frequencies are higher in the DCM patients who have a better cardiac function (The LVEF values are higher, and the grading of cardiac function is better).2. The MCP-1-2518G/G genotype frequencies are higher in the DCM patients who have a VMC medical history.3. The CCR2-64I mutation frequencies are higher in the DCM patients who have a better cardiac function (the LVEF values are higher, the grading of cardiac function is better and the cardiac rhythm normal) and non-VMC medical history.4. The SDF-1 3'A, MCP-1-2518G/A and CCR2-64I have a certain significance in evaluate DCM patients'prognosis, suggesting the possible role in the process of cardiac function injury in DCM patients with which the SDF-1, MCP-1 and CCR2 may be concerned.
Keywords/Search Tags:Gene Polymorphism, SDF-1, MCP-1, CCR2, CCR5, Mutation, Dilated cardiomyopathy
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