Relationship Between Fibrinogen Gene β-455G/A,Arg448Lys Polymorphisms And Plasma Fibrinogen Concentration,Lowerextremity Deep Venous Thrombosis

Objective: To investigate the relationship between Fibrinogen Geneβ-455G/A (FGB-455G/A),Arg448Lys(FGB 448G/A) Polymorphisms and Plasma Fibrinogen Concentration,Lowerextremity Deep Venous Thrombosis.Methods: In order to undertake a case-control study,153 LEDVT hospitalized patients diagnosed by angiography (case group) and 262 subjects without LEDVT (control group) in Fujian provincial hospital were studied. Basic clinical data such as age,gender,Body mass index(BMI) were collected. Biochemical parameters such as Triglyceride(TG), Cholesterol(CHOL), High density lipoprotein(HDL), Low density lipoprotein(LDL), Fasting blood glucose(GLU) and plasma fibrinogen concentration (Fg) were measured. Polymerase chain reaction(PCR) and Restriction fragment length polymorphism(RFLP) were used to characterize FGB-455G/A and FGB 448G/A genotypes. All of the genotypes were checked by DNA sequencing. SSPS 13.0 was used to analyze all the data.Result: 1.The levels of BMI and plasma fibrinogen concentration had significant differences between two groups (P<0.05), and both were higher in case group;the levels of age,gender, Triglyceride, Cholesterol, High density lipoprotein, Low density lipoprotein, Fasting blood glucose had no significant differences between two groups (P>0.05). 2.The distributions of FGB-455G/A,FGB 448G/A genotypes between case group and control group were under the assumption of the Hardy-Weinberg equilibrium by non-parametricχ2 test (P>0.05). 3.χ2 test showed that the distributions of FGB-455G/A genotypes and alleles had significant differences between two groups. 455AA+AG genotype frequency and A-455 allele frequency were higher in case group than the ones in control group (P<0.05). 4.χ2 test showed that the distributions of FGB 448G/A genotypes and alleles had significant differences between two groups. 448AA+AG genotype frequency and A-448 allele frequency were higher in case group than the ones in control group (P<0.05) . 5.The plasma fibrinogen concentration had significant difference between FGB-455G/A genotypes (P<0.05) and plasma fibrinogen concentration in 455AA+AG genotype group was higher than it in 455GG genotype group. The plasma fibrinogen concentration had no significant difference between FGB 448G/A genotypes (P>0.05). 6.Binary logistic regression showed that,by adjusting other confounding factors,the factors entered the final equation were:Fg(OR=1.718),BMI(compared with low weight group,normal weight group OR1=3.490,overweight group OR2=5.881,obesity group OR3=7.893),455AA+AG genotype(OR=1.739),448AA+AG genotype(OR=2.527)。7.Crossover analysis showed that, compared with subjects who were not exposed to risks, OREG of those have 455AA+AG genotype and BMI≥24 kg/m2 was 4.82;OREG of those have 448AA+AG genotype and BMI≥24 kg/m2 was 6.16.Conclusions: 1.Increase of plasma fibrinogen concentration might be an independent risk factor for LEDVT. 2. High BMI might be associated with LEDVT. 3.FGB-455G/A genotypes were associated with the plasma fibrinogen concentration. Subjects carrying 455AA+AG genotypes tend to be more susceptible to higher Fg concentration, and the A-455 allele was associated with the plasma fibrinogen concentration. There is no evidence to demonstrate that FGB 448G/A genotypes were associated with the plasma fibrinogen concentration. 4.FGB-455G/A genotypes were associated with LEDVT respectively. Subjects carrying 455AA+AG genotypes tend to be more susceptible to LEDVT, and the A-455 allele might be a genetic risk factor for LEDVT. 5.FGB 448G/A genotypes were associated with LEDVT respectively. Subjects carrying 448AA+AG genotypes tend to be more susceptible to LEDVT, and the A-448 allele might be a genetic risk factor for LEDVT.