| Elevation of plasma fibrinogen concentration is a major risk factor for coronary heartdisease, stroke, and peripheral artery disease. There is evidence that genetic variation in the Bp-fibrinogen gene contributes to the rate of synthesis of fibrinogen, but the underlying molecular mechanism of the genetic heritability of plasma concentration is largely unknown. The polymorphism of two common nucleotide substitutions at positions -148C/T, -455G/A from the transcriptional start sites in the promoter region of the p-fibrinogen gene and another nucleotide substitution -448G/A in the 8th exon were evaluated in this study. The distribution of the three site variants in patients with coronary heart disease (CHD) and stroke was investigated, and their association with plasma fibrinogen level was analyzed.Purpose:To evaluate the polymorphism of different alleles in fibrinogen BP-455G/A> -148C/T and -448G/A sites, their distributive characteristics in patients with coronary artery disease and stroke and the relationship of these genetic variants with plasma fibrinogen levels.Materials and methods:150 patients admitted into our hospital from August 2001 to March 2002 were enrolled. These patients were divided into three groups. The first group included 50 patients who suffered from coronary heart disease. The second group included 48 patients with cerebral infarction. And the other included 52 patients exclusive of thrombotic disease. Lymphocytes in peripheral blood were separated by dissolution of red blood cells in low-saturation solution, and genomic DNA was extracted from the lymphocytes with hydroxybenzene -chloroform method. Polymerase chain reaction technique was used to amplify objective gene. And relatively restriction nucleotide endonuclease was used to digest PCR production. The digested products were showed by ultraviolet after horizontal gel electrophoresis and each genotype was analysised. Statistical Package for the Social Sciences (SPSS 11.0) for windows was used for data analysis.Result:1. Allele distribution of fibrinogen Bp-455G/A, -448G/A and -148C/T in CHD group and stroke group was significantly different from that in non-thrombotic controls, P<0.05.2. In CHD group, stroke group and non-thrombotic group, H2 allele frequency of BP-455G/A was 0.27, 0.27 and 0.16 ; A allele frequency of Bp-448 G/A was 0.30, 0.27 and 0.15 respectively; and T allele frequency of BP-148 C/T was 0,32, 0.29 and 0.14 respectively.3. Comparing the plasma fibrinogen level between the different genotype subgroups in CHD, stroke and control groups, a significantly higher plasma fibrinogen concentration was founded in subgroups of H1H2+H2H2 genotype of-455G/A and CT+TT genotype of-148C/T than that in H1H1 and CC genotype subgroups. But a significantly higher plasma fibrinogen level in GA+AA genotype subgroup of -448G/A site was detected only in stroke group.4. Genotype polymorphism of-455G/A site and -148C/T sites was consistent completely in 132 cases, accounting for 88% of all studied cases. And polymorphism consistence of -445G/A with -448G/A was 47.33%, and -448G/A with -148C/T was 48.67%.5. The plasma fibrinogen level was increased with the variant numbers of genotype polymorphism, either in all cases or in different disease groups.Conclusion:1. Allele distribution of fibrinogen B(3-455G/A and -148C/T was significantly associated with plasma fibrinogen level. Fibrinogen level increased in subgroups with genotype variation.2. BP-455G/A site of fibrinogen gene is in completely disequilibrium-linkage with -148C/T site. But the linkage of-448G/A with -455G/A and -148C/T was not so strong.3. The plasma fibrinogen level was increased with the variant numbers of genotype polymorphism.4. The variation frequency of flbrinogen genotype polymorphism in CHD and Stroke group was significantly higer than that in control group, accompanying with a higher plasma flbrinogen level.5. Genotype of flbrinogen B(J-445G/A -448G/A a...
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