We have identified a genetic polymorphism of factor VII that is strongly associated with plasma factor VII coagulant activity (factor VIIc) in healthy individuals from the United Kingdom. This polymorphism was detected after Msp I digestion of polymerase chain reaction-amplified genomic DN A. In a sample of 284 men, the frequency of the M2 allele (loss of cutting site) is 0.1, and individuals with the M1M2 genotype have factor VIIc levels 22% below the sample mean (p<0.0001). F actor VII is a serine protease found in plasma and is one of the vitamin K-dependent coagulation factors, along with prothrombin (factor II), factors IX and X, and proteins C and S (for review, see Reference 1). Factor VII is synthesized principally in the liver and is secreted as a single-chain glycoprotein of apparent M, 48,000. 2Cleavage of human factor VII to factor Vila, a two-chain form held together by disulfide bonds, results in a 20-to 25-fold increase in enzyme activity.2 This cleavage can be effected by a number of activated coagulation factors, including factors Xlla, Xa, and IXa and thrombin.2 In the presence of tissue factor and calcium ions, factor Vila converts factor X to factor Xa in the initiating reaction of the extrinsic coagulation pathway.

SummaryWe investigated the association between fibrinogen levels and a HaeIII restriction fragment length polymorphism located at −453 bp from the start of transcription of the β fibrinogen gene. 292 healthy men aged 45 to 69 years, recruited from general practices throughout Britain, were studied. None had a history of ischaemic heart disease. 41.1% (120) were smokers and fibrinogen levels were higher in this group. The frequency of the noncutting allele (designated H2) was 0.19 and was the same in smokers and non-smokers. The H2 allele was associated with elevated levels of fibrinogen in both smokers and non-smokers and the effect of genotype was similar in both groups. After smoking, HaeIII genotype was the strongest predictor of fibrinogen levels and explained 3.1% of the variance in fibrinogen levels. These results confirm earlier studies that variation at the fibrinogen locus contributes to the between-individual differences in plasma fibrinogen level.

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