Genetic variation at fibrinogen loci and plasma fibrinogen levels.

In view of the controversy regarding genetic variation at the fibrinogen loci and plasma fibrinogen levels, we have analysed DNA polymorphisms at the alpha (TaqI), beta (BclI and HaeIII), and gamma (KpnI/SacI) fibrinogen loci in 247 subjects whose plasma fibrinogen was determined by clotting and nephelometric assays. Strong linkage disequilibrium was found between the alpha/TaqI and gamma/KpnI/SacI markers and between the beta/BclI and beta/HaeIII markers. A lesser association was found between the alpha/TaqI and beta/BclI loci, beta/BclI and gamma/KpnI/SacI markers, alpha/TaqI and beta/HaeIII markers, and the gamma/KpnI/SacI and beta/HaeIII markers. This is consistent with the known physical order of these loci and suggests a relative excess of recombination in the alpha/gamma to beta interval. Plasma fibrinogen levels, by either assay method, when corrected or uncorrected for age, sex, and smoking habit, did not show any statistically significant associations with the four fibrinogen polymorphisms examined at the alpha, beta, and gamma fibrinogen loci either singly or when analysed as a haplotype.