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The Relationship Between Gene Polymorphisms Of FVII And Coronary Heart Disease In Henan Han Population

Posted on:2008-11-11Degree:MasterType:Thesis
Country:ChinaCandidate:W YangFull Text:PDF
GTID:2144360215461548Subject:Internal Medicine
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Background and objectiveCoronary heart disease(CHD) is one of the main etiologies and death causes that threaten people's health seriously. Studies have shown that hyperlipidemia, hypertension, cigarette smoking, diabetes mellitus and family history of cardiovascular disease are the classic risk factors of CHD, however, not all patients who develop coronary heart disease have such risk factors. Some studies have found that evolvement and progression of CHD are influenced by hypercoagulation state which caused by the abnormity of coagulation factors.Factor VII (FVII) is a main initiation factor of physiological and pathological blood clotting reaction, whith is the first enzyme in the extrinsic pathway of the blood coagulation system, and participates the intrinsic coagulation pathway. Some studies have found the relationship between FVII level and CHD, and plasma FVII level is influenced by genetic and environmental factors. So there are some studies that directly research on the association of FVII gene polymorphisms with CHD , however ,there are different results in these studies, because of the difference of geography and sample size.In order to study the relationship of FVII genetic polymorphisms and CHD in Henan Han population, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or PCR was adopted to study whether the R353Q, 5'F7, IVS7 polymorphisms are associated with CHD , MI, the number of diseased vessels and the classic risk factors of CHD in Henan Han population. The combining roles of the three polymorphisms was also investigated.Study population1 Patients 419 unrelated patients with CHD( 290 men and 129 women, mean age 60.1±10.2 years) was investigated . All patients were selected from the department of cardiology of the First Affiliated Hospital of Zhengzhou University, and 243 cases underwent coronary angiography. All of them are Han population.2 Controls The 564 unrelated healthy controls were selected from subjects in outpatient department who underwent regular check-up examination (362 men and 202 women , mean age 62.7±11.7 years). The controls had no history of cardiovascular disease, DM. All of them are Han population.MethodsPeripheral venous blood samples were collected. Genomic DNA was extracted from leukocytes .Three polymorphisms of FVII genes were analyzed by PCR-RFLP or PCR.Statistical analysisGenotype and allelic frequencies were estimated by the gene-counting method and compared using the x~2 test. Hardy-Weinberg equilibrium was confirmed with the X~2 test. All statistical analysis were performed with SPSS 11.01 software.Results1 Relationship between genetic polymorphisms and CHD1. 1 The genotype distribution of the R353Q, 5'F7 and IVS7 polymorphisms was compatible with the Hardy-Weinberg equilibrium in the CHD group and Controls .1. 2 There were three kinds of genotype of R353Q:RR,RQ and QQ in Henan Han population. The distribution of genotype and allelic frequencies between CHD group and controls displayed no significant difference(OR 0.753,95%CI 0.508-1.118), the same as between MI group and controls (OR 0.854, 95%CI 0.541-1.349).1. 3 There were three kinds of genotype of 5'F7:P0P0, P0P10, P10P10 in Henan Han population. There was a significant difference in the frequencies of genotype and allele between CHD group and controls (OR 0.469, 95%CI 0.280-0.787) ,the same as between MI group and controls(OR 0.375, 95%CI 0.118-0.748). The frequency of P10 allele carriers was significantly lower in study groups than that in controls.1.4 There were many kinds of genotype of IVS7,such as H7H7,H7H6,H6H6,H6H5,H7H5,H8H6,H8H7 in Henan Han population. There was a significant difference in the frequencies of genotype between CHD group and controls(OR 0.645, 95%CI 0.483-0.861) ,the same as between MI group and controls(OR 0.617, 95%CI 0.442-0.861).1. 5 There was a signification relationship between combining genetypes (R353Q and 5'F7, 5'F7 and IVS7, the three genetic polymorphisms)and CHD,MI.OR of the combining protective genetypes to CHD is 0.337(95%CI 0.180—0.629), 0.512 (95% CI 0.288—0.912), 0.384(95%CI 0.194—0.762),respectively,and OR of these to MI is 0.397(95%CI 0.192—0.822), 0.353(95%CI 0.157—0.797), 0.415(95%CI 0.183—0.945) ,respectively. But combining R353Q and IVS7 had not the association withCHD, ML2 Relationship between genetic polymorphisms and the number of diseased vessels in the CHD groupThere was no significant relationship between FVII genetic polymorphisms and the number of diseased vessels(R353Q: x~2=3.367, P>0.05; 5'F7: x~2=1.728, P>0.05; IVS7:x~2=1.663,P>0.05).3 Relationship between genetic polymorphisms and classic risk factors of CHDThere were no differences among the genotypes of the R353Q and IVS7 polymorphisms in terms of sex, diabetes mellitus, hyperlipidemia, hypertension, cigarette smoking, family history of cardiovascular and et al. But a significant relationship was found between the 5'F7 polymorphism and hypertension.Conclusion1 There are the FVII R353Q, 5'F7, IVS7 polymorphisms in Henan Han population. The frequent genetypes of every position can be found. The distribution of these genetic polymorphisms may exist racial differences.2 In Henan Han population , the R353Q polymorphism may not be an independent genetic risk factor of CHD and MI. Its genotype is not associated with the number of diseased coronary artery.3 In Henan Han population, the 5'F7 polymorphism may be an important risk factor of CHD and MI. The mutation may be protective against CHD and MI. Its genotype is not associated with the number of diseased coronary artery .4 In Henan Han population , the IVS7 polymorphism may be an important risk factor of CHD and MI . The H7 allele may be protective against. CHD and MI. Its genotype is not associated with the number of diseased coronary artery .5 There is a signification relationship between combining genetypes (R353Q and 5'F7, 5'F7 and IVS7, the three genetic polymorphisms)and CHD,MI. But the combining R353Q and IVS7 has not the association with CHD, MI.6 In the CHD patients of Henan Han , the 5'F7 polymorphism may be associated with hypertention.
Keywords/Search Tags:factor VII, gene, genetic polymorphism, coronary heart disease
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