title: Platelet receptor gain-of-function single nucleotide polymorphisms in carotid and vertebral stenosis patients.
abstract: The role of platelet receptor gain-of-function single nucleotide polymorphisms (SNP) in cardiovascular disease is controversial. We hypothesised that certain SNPs may accelerate the development of carotid artery stenosis. The intronic PAR-1 receptor intervening sequence-14 A/T (IVSn-14 A/T) polymorphism and three additional platelet receptor polymorphisms, i.e. GPIa (807C/T), GPIbα (5T/C) and HPA-1a/HPA-1b (Pl (A1/A2)) of GPIIIa were studied. The interaction of SNPs with conventional risk factors including male gender, hypertension, high cholesterol, diabetes, advanced age and smoking were investigated. The hypothesis was tested in 114 well-characterised patients with symptomatic carotid or vertebral stenosis from the British CAVATAS population and compared the results with 97 unrelated controls. The allele frequency of the platelet gain-of-function SNP was not significantly different in the CAVATAS population as compared to controls (PAR-1A/T (P = 0.13), GPIa C/T (P = 0.25), GPIIIa HPA-1a/HPA-1b (PlA1/A2) (P = 0.66) and GPIb T/C (P = 0.20)). In the subgroup of smokers, however, the prothrombotic GPIbα C mutated allele was found in a significantly higher frequency in the patient as compared to the control group (P = 0.04). Contrary to the primary hypothesis, the PAR-1A/T SNP as well as the other SNPs tested were not over- or underrepresented in the CAVATAS population. However, a significantly increased prevalence of GPIb-α (5C/T) was found in the subgroup of smokers and may represent an important cofactor in this patient group of our hypothesis-generating study.
authors.affiliation: Department of Medicine, Cantonal Hospital Baden, 5404 Baden, Switzerland.
authors.forename: Andrea Kopp
authors.initials: AK
authors.lastname: Lugli
authors.forename: Martin M
authors.initials: MM
authors.lastname: Brown
authors.forename: Jan
authors.initials: J
authors.lastname: Steffel
authors.forename: Linda
authors.initials: L
authors.lastname: Büchi
authors.forename: Dorothee
authors.initials: D
authors.lastname: Förnzler
authors.forename: Annabelle
authors.initials: A
authors.lastname: Dupont
authors.forename: Pascale
authors.initials: P
authors.lastname: Gaussem
authors.forename: Marc
authors.initials: M
authors.lastname: Forestier
authors.forename: Juerg H
authors.initials: JH
authors.lastname: Beer
mesh_terms: D000367:Age Factors; D000368:Aged; D016893:Carotid Stenosis / Q000235:genetics* / Q000628:therapy; D004843:Epistasis, Genetic; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010980:Platelet Membrane Glycoproteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012737:Sex Factors; D006113:United Kingdom; D014715:Vertebrobasilar Insufficiency / Q000235:genetics* / Q000628:therapy
chemical_list: D010980:Platelet Membrane Glycoproteins