POLYMORPHISMS OF FACTOR-V, FACTOR-VII, AND FIBRINOGEN GENES - RELEVANCE TO SEVERITY OF CORONARY-ARTERY DISEASE

We explored the associations between G-->A mutations of factor V and f actor VII genes and the Hae III polymorphism of the fibrinogen gene an d the severity of coronary artery disease (CAD), as assessed angiograp hically in 545 white Australian patients (388 male and 157 female) age d less than or equal to 65 years. We also assessed the relations with other potentially atherogenic variables. Elevated fibrinogen levels we re associated with more severe CAD (P<.05), but none of the factor V, factor VII, and fibrinogen DNA variants were predictive of CAD severit y, as assessed by the number of significantly diseased vessels (>50% l uminal obstruction). The rare allele frequencies of factor V (A allele ), factor VII (M2 allele), and fibrinogen (H2 allele) were .025, .114, and .201 for men and .022, .077, and .169 for women, respectively, an d were not different from those in healthy whites. In the patient popu lation, there was a strong, positive association between lifetime smok ing dose (in pack-years) and circulating fibrinogen levels (r=.184, P= .001). This association was stronger than that between current smoking habit and fibrinogen and is consistent with a dosage effect. However, there was no significant contribution of fibrinogen genotype to fibri nogen levels in this patient population. We conclude that elevated fib rinogen levels are associated not only with the occurrence of CAD but also with more severe CAD and that measurement of DNA variants of the factor V, factor VII, and fibrinogen genes that we assessed may not pr ovide information in predicting CAD severity in addition to that obtai ned by measuring circulating levels of the relevant clotting factors. There is, moreover, a positive dosage effect (in pack-years) of smokin g on circulating fibrinogen levels.