[Polymorphism frequency of fibrinogen Bβ-chain 448Arg and Lys, and the differences of plasma fibrinogen level and clotting function with three genotypes in Japanese].

The 448th residue in the fibrinogen Bβ-chain molecule is known to be polymorphic (Arg/Lys, R/K), and its allele frequency was previously estimated to be R: 0.85 and K: 0.15 in the US. In the present study, we collected blood samples from 64 healthy individuals and examined the frequency of the fibrinogen Bβ-chain 448 polymorphism in the Japanese population as well as the relationship between polymorphic types and the function and levels of fibrinogen. The polymorphic site was confirmed by MnlI restriction analysis and direct sequencing analysis for amplified 860 bp PCR products containing the Bβ 448 residue. Fibrinogen plasma levels were estimated based on functional and immunological methods. Functional analyses were performed on the R/R, R/K, and K/K types using thrombin-catalyzed fibrin polymerization. The R/R type was detected in 48 out of 64 subjects, R/K in 15, and K/K in one. Therefore, the allele frequency was found to be R: 0.87 and K: 0.13 for the Bβ 448 site, which was similar to that reported previously in the US. The polymorphism did not affect fibrinogen plasma levels. The results of the analysis on fibrin polymerization of the three types suggested that lateral aggregation may be significantly slower in the fibrinogen Bβ-chain 448R/K and K/K types than in the R/R type. (Original).