Relationship of the platelet glycoprotein PlA and fibrinogen T/G+1689 polymorphisms with peripheral arterial disease and ischaemic heart disease in the Edinburgh Artery Study

Introduction: Genetic variation in plasma fibrinogen and the platelet receptor GP ilia locus has been independently associated with increased risks of ischaemic heart disease, but there have been few reports on the relationship with peripheral arterial disease. This study determined the risk of peripheral arterial disease and ischaemic heart disease associated with polymorphisms of fibrinogen T/G(+) (1689) and platelet glycoprotein pl(A) genes and the effects of cigarette smoking and fibrinogen. Materials and methods: In the 5-year follow-up phase of the Edinburgh Artery Study, 939 subjects (60-79 years) had DNA extracted from a venous blood sample. One hundred sixteen subjects were identified as having angina, 87 a myocardial infarction, 104 had intermittent claudication and 663 subjects comprised a healthy group. Results: Distribution of the fibrinogen genotype was similar across the disease and healthy groups. Logistic regression analyses found no significant association between fibrinogen genotype and ischaemic heart disease and peripheral arterial disease. A lower percentage of claudicants had the pl(A2) allele (8.3% vs. 15.2%, p = 0.025). After adjustment for age and sex, the risk of IC associated with the pl(A2) was half that of the homozygous Pl(A1) genotype (OR 0.49, 95% CI 0.25, 0.88;p less than or equal to 0.05). Adjustment for lifetime smoking and fibrinogen levels increased the odds slightly to nonsignificance. Conclusions: The pl(A2) genotype was associated with a decreased risk of developing IC. There was no significant relationship between fibrinogen T/G(+) (1689) genotype and ischaemic heart disease and peripheral heart disease in this older population. (C) 2004 Elsevier Ltd. All rights reserved.