Relationship of the platelet glycoprotein PlA and fibrinogen T/G+1689 polymorphisms with peripheral arterial disease and ischaemic heart disease.
BACKGROUND
Genetic variation in plasma fibrinogen and the platelet receptor GP IIIa 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.


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<==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 and peripheral heart disease in this older population.
Wolfson Unit for Prevention of Peripheral Vascular Diseases, Department of Community Health Sciences, University of Edinburgh Medical School, Teviot Place, Edinburgh EH8 9AG, UK. Flick.Smith@ed.ac.uk
Felicity B
FB
Smith
J Michael
JM
Connor
Amanda J
AJ
Lee
Alexander
A
Cooke
Gordon D O
GD
Lowe
Ann
A
Rumley
F Gerald
FG
Fowkes
D000368:Aged; D000787:Angina Pectoris / Q000097:blood / Q000235:genetics; D015703:Antigens, CD / Q000235:genetics; D000954:Antigens, Surface / Q000235:genetics*; D001157:Arterial Occlusive Diseases / Q000097:blood / Q000235:genetics*; D003430:Cross-Sectional Studies; D005260:Female; D005340:Fibrinogen / Q000235:genetics*; D006801:Humans; D007383:Intermittent Claudication / Q000097:blood / Q000235:genetics; D037181:Lectins, C-Type / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000235:genetics; D017202:Myocardial Ischemia / Q000097:blood / Q000235:genetics*; D055651:NK Cell Lectin-Like Receptor Subfamily B; D016491:Peripheral Vascular Diseases / Q000097:blood / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D012606:Scotland; D012907:Smoking
D015703:Antigens, CD; D000954:Antigens, Surface; C527203:KLRB1 protein, human; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D005340:Fibrinogen