The genetics of haemostasis: a twin study

Background The concentrations of fibrinogen, factor VII and VIII, von Wille brand factor, plasminogen activator inhibitor-1 (PAI-1), and tissue plasmin ogen activator have been associated with coronary-heart disease. In additio n, polymorphisms in the genes coding for fibrinogen, factor VII, PAI-1, and factor XIII have been reported to affect both protein concentrations and c ardiovascular disease risk. Methods We did a classic twin study to assess heritabilities of these haemo static factors. We enrolled 1002 female twins; 149 pairs of monozygotic and 352 pairs of dizygotic twins. 89 monozygotic and 196 dizygotic twin pairs were analysed for factor VII. Findings Quantitative genetic model fitting showed that genetic factors con tributed to about 41-75% of the variation in concentrations of fibrinogen, factor VII, factor VIII, PAI-1, tissue plasminogen activator, factor XIII A -subunit and B-subunit, and von Willebrand factor. Factor XIII activity sho wed higher (82%) and factor Xlla lower (38%) heritability. Interpretation We have shown that genetic factors have a major effect on pl asma concentrations of haemostatic proteins. Our results stress the importa nce of research into the genetic regulation of proteins involved in haemost asis and atherothrombotic disorders, including myocardial infarction and st roke.