The role of fibrinogen in cardiovascular disease has been extensively studi
ed, and meta-analyses have definitively confirmed that high levels of fibri
nogen are associated with an increased risk of the disease. In recent years
, several polymorphisms have been identified in the fibrinogen chain genes
that contribute to determine the levels of fibrinogen in the general popula
tion. The fibrinogen beta -chain gene has been more extensively studied bec
ause the beta -chain synthesis is the limiting step in the production of ma
ture fibrinogen. Overall, the studies show an association between beta -fib
rinogen chain polymorphisms and the levels of fibrinogen. In contrast, the
majority of the studies did not find any relation with the risk of cardiova
scular disease. The individual responses to gender or to environmental stim
uli such as smoking, physical exercise, or infections may be genetically de
termined, and genetic variability underlies changes in biological reactions
that contribute to differences in cardiovascular risk. In the future, gene
-environment interactions should be considered in evaluating the relevance
of genetic variations on the risk of cardiovascular disease.