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

Abstract

Four novel polymorphisms were identified in the fibrinogen gene cluster. Three of them were localized in the promoter regions of the Aalpha-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 (gamma 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 increased risk of cardiovascular disease and genetic variations have been evaluated as thrombotic risk predictors, we analyzed their role in determining the plasma levels of this protein. Owing to the low frequency of the rare allele of alpha -128 C/G and gamma -239 A/G polymorphisms, association with plasma fibrinogen levels was investigated for only alpha -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 significant association with plasma fibrinogen levels was found.

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