title: KNG1 Ile581Thr and susceptibility to venous thrombosis.
abstract: Three single nucleotide polymorphisms (SNPs) were recently found to be associated with activated partial thromboplastin time (aPTT). Because shortened aPTT levels have been observed in patients experiencing venous thrombosis (VT), we investigated the effects of these 3 aPTT-associated SNPs, rs2731672, rs9898, and rs710446, on the risk of VT in a sample of 1110 healthy patients and 1542 patients with VT. Among the 3 tested SNPs, only rs710446 was associated with VT risk; the rs710446-C allele was associated with an increased risk of VT (odds ratio 1.196, 95% confidence interval 1.071-1.336, P = .0012). This association also was observed in an independent sample of 590 controls and 596 patients (odds ratio 1.171, 95% confidence interval 0.889-1.541, P = .059). We also confirmed that the rs710446-C allele was associated with decreased aPTT levels, making this nonsynonymous Ile581Thr variant a new genetic risk factor for VT.
authors.affiliation: INSERM UMR_S 626, Laboratory of Haematology, CHU Timone, 246 rue Saint-Pierre, Marseille Cedex 05, France. pierre.morange@ap-hm.fr
authors.forename: Pierre-Emmanuel
authors.initials: PE
authors.lastname: Morange
authors.forename: Tiphaine
authors.initials: T
authors.lastname: Oudot-Mellakh
authors.forename: William
authors.initials: W
authors.lastname: Cohen
authors.forename: Marine
authors.initials: M
authors.lastname: Germain
authors.forename: Noémie
authors.initials: N
authors.lastname: Saut
authors.forename: Guillemette
authors.initials: G
authors.lastname: Antoni
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Alessi
authors.forename: Marion
authors.initials: M
authors.lastname: Bertrand
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Dupuy
authors.forename: Luc
authors.initials: L
authors.lastname: Letenneur
authors.forename: Mark
authors.initials: M
authors.lastname: Lathrop
authors.forename: Lorna M
authors.initials: LM
authors.lastname: Lopez
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Lambert
authors.forename: Joseph
authors.initials: J
authors.lastname: Emmerich
authors.forename: Philippe
authors.initials: P
authors.lastname: Amouyel
authors.forename: David-Alexandre
authors.initials: DA
authors.lastname: Trégouët
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution / Q000235:genetics / Q000502:physiology; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007532:Isoleucine / Q000235:genetics; D007704:Kininogens / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D013912:Threonine / Q000235:genetics; D020246:Venous Thrombosis / Q000235:genetics*
chemical_list: D007704:Kininogens; D007532:Isoleucine; D013912:Threonine