Editor—Several prospective epidemiological studies have consistently shown that raised plasma fibrinogen is an independent risk factor for coronary heart disease (CHD).1-4 Clinical studies have also confirmed that plasma fibrinogen levels are related to the extent of coronary atherosclerosis in CHD patients.5-7 Two other studies showed that raised fibrinogen level is an independent risk factor for mortality among male CHD patients.8 9

Plasma fibrinogen is an acute phase protein, levels of which rise rapidly in response to infection, inflammation, injury, or other trauma.10 Many other environmental factors are also associated with increased plasma fibrinogen levels. They include age, obesity, blood cholesterol, lipoprotein,11-13hypertension,1 diabetes mellitus,14 and for women use of oral contraceptives and menopause.11 12 Diet does not influence fibrinogen levels, whereas smoking can dramatically increase them.11 12 This is dose dependent1 15 and is reversible on cessation of smoking.11 Moreover, it has been observed that a substantial part of the relationship between smoking and ischaemic heart disease is mediated through the effect of smoking on plasma fibrinogen levels.3

The genetic contribution to plasma fibrinogen levels has been widely investigated. The heritability of fibrinogen has been estimated to be 0.51 by path analysis.16 Two twin studies estimated heritability to be 0.29-0.30.17 18 Several restriction fragment length polymorphisms (RFLPs) of the fibrinogen gene are known to influence plasma fibrinogen level. A −455G/A RFLP at the promoter region (β gene) has been found to be associated with differences of fibrinogen levels in several white populations.19-23Another β gene −148C/T RFLP accounted for 4% of the total variance of fibrinogen levels in an American population.24 In two British studies, the percentage of fibrinogen variance that could be explained by a BclI RFLP at the 3′ …