Identification of four novel polymorphisms in the A alpha and gamma fibrinogen genes and analysis of association with plasma levels of the protein

Four novel polymorphisms were identified in the fibrinogen gene cluster. Th ree of them were localized in the promoter regions of the Aa-chain (alpha - 128 C/G, alpha - 58 G/A) or the gamma -chain (gamma - 239 A/G) gene, while the remaining one was identified in intron 9 of the gamma -chain gene (gam ma 7792 C/T). Genotype distributions for these polymorphisms were analyzed in 200 healthy Italian individuals and were in Hardy-Weinberg equilibrium. Since high levels of plasma fibrinogen have been associated with an increas ed risk of cardiovascular disease and genetic variations have been evaluate d as thrombotic risk predictors, we analyzed their role in determining the plasma levels of this protein. Owing to the low frequency of the rare allel e of alpha - 128 C/G and gamma - 239 A/G polymorphisms, association with pl asma fibrinogen levels was investigated for only a - 58 G/A and gamma 7792 C/T. We also investigated in the same population two previously identified polymorphisms in the fibrinogen gene cluster (alpha TaqI and beta - 455 G/A ) chosen for their widely studied association with plasma fibrinogen levels . In the multivariate linear regression analysis, no statistically signific ant association with plasma fibrinogen levels was found. (C) 2001 Elsevier Science Ltd. All rights reserved.