title: Complex association of protein C gene promoter polymorphism with circulating protein C levels and thrombotic risk.
abstract: The allele and haplotype frequency of the -1654 C/T and -1641 A/G protein C (PC) gene promoter polymorphisms was determined and analyzed according to circulating PC concentrations in 394 healthy subjects aged 20 to 60 years. The CG haplotype was associated with a lower PC concentration in both homozygous and heterozygous subjects compared with noncarriers. The TA allele had the reverse effect, but only in homozygotes. The distribution of the CG and TA alleles was significantly different in 242 patients, aged 17 to 60 years, with venous thromboembolism. The CG allele increased the risk of thrombosis, with an OR of 1.39 (95% confidence interval (CI), 1.04 to 1.87). The TA allele was protective in subjects aged <45 years, with an OR of 0.68 (95% CI, 0.44 to 1.04). TA was also significantly associated with older age at the first thrombosis. This study confirms the link between the PC gene promoter and circulating PC levels, and suggests a complex effect on the risk of thrombosis.
authors.affiliation: Unité INSERM 428, Unité INSERM 258, and Centre Claude Bernard de Recherche sur les Maladies Vasculaires, Hôpital Broussais, Paris 14e. martine.aiach@brs.ap-hop-paris.fr
authors.forename: M
authors.initials: M
authors.lastname: Aiach
authors.forename: V
authors.initials: V
authors.lastname: Nicaud
authors.forename: M
authors.initials: M
authors.lastname: Alhenc-Gelas
authors.forename: S
authors.initials: S
authors.lastname: Gandrille
authors.forename: E
authors.initials: E
authors.lastname: Arnaud
authors.forename: J
authors.initials: J
authors.lastname: Amiral
authors.forename: L
authors.initials: L
authors.lastname: Guize
authors.forename: J N
authors.initials: JN
authors.lastname: Fiessinger
authors.forename: J
authors.initials: J
authors.lastname: Emmerich
mesh_terms: D000328:Adult; D000483:Alleles; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011486:Protein C / Q000032:analysis / Q000235:genetics*; D012306:Risk; D013927:Thrombosis / Q000209:etiology*
chemical_list: D011486:Protein C