Linkage disequilibrium relationships among four polymorphisms within the human fibrinogen gene cluster

The extent of linkage equilibrium was estimated among four recently characterized human fibrinogen restriction fragment length polymorphisms (RFLPs) using a randomly selected group of 110 individuals from California. Two coding region RFLPs, RsaI and MnlI (FGA codon 312 and FGB codon 448, respectively), and two RFLPs located in the 5' flanking region of the FGB gene, AluI (HindIII) and HaeIII, were analyzed. Maximum likelihood estimates based on genotypic data indicated that the RsaI polymorphism in the FGA gene was at apparent linkage equilibrium with the MnlI, AluI, and HaeIII sites in the FGB gene, but strong linkage disequilibrium was noted for the MnlI-AluI, MnlI-HaeIII, and AluI-HaeIII RFLP pairs within the latter gene. The discrepancy in disequilibrium relationships among these closely linked RFLPs may indicate a region of increased recombination between the FGA and FGB RFLP loci. The FGA RsaI polymorphism, when used in conjunction with any of the FGB sites examined, will provide more detailed linkage or association data than analyses that would utilize only FGB sites. Effective use of polymorphisms within the fibrinogen locus will aid analysis of the relationships between fibrinogen genotype, plasma fibrinogen levels, and risk of cardiovascular disease.