title: Thrombotic risk according to SERPINC1 genotype in a large cohort of subjects with antithrombin inherited deficiency.
abstract: Inherited quantitative (type I) or qualitative (type II) antithrombin deficiency (ATD) due to mutations in the SERPINC1 gene is a well-known risk factor for venous thromboembolism. ATD may also increase risk for arterial thrombosis. Few studies have investigated risk for thrombosis according to mutations. We addressed this topic in a large retrospective cohort study of 540 heterozygous carriers of SERPINC1 mutations and compared risk for first venous or arterial thrombosis associated with carrying of different type II or type I mutations. No clear difference in risk for first venous thrombotic event was observed among type I (missense or null), type IIRS or type IIPE mutation carriers except for a few variants that displayed lower risk [all events, adjusted relative risk: Cambridge II: 0.42 (95 %CI 0.25-0.70), Dublin: 0.35 (95 %CI 0.13-0.99)]. IIHBS mutation carrying was associated with a clearly lower risk than type I mutation carrying [0.28 (95 %CI 0.20-0.40)]. These differences in risk were observed for both all venous thrombotic events and pulmonary embolism associated with deep venous thrombosis. The HBS group was also heterogeneous, with AT Budapest 3 carriers displaying a non-significantly different risk [0.61 (95 %CI 0.31-1.20)] compared to type I mutation carriers. We also studied risk for arterial thrombosis and found no significant influence of mutation type. Altogether, our findings suggest a place for SERPINC1 genotyping in the diagnosis of ATD.
authors.affiliation: M. Alhenc-Gelas, Laboratoire d'Hématologie, HEGP, 20 Rue Leblanc, 75015 Paris, France, Tel: +33 156093901, Fax: +33 156093393, E-mail: martine.alhenc-gelas@aphp.fr.
authors.forename: Martine
authors.initials: M
authors.lastname: Alhenc-Gelas
authors.forename: Genevieve
authors.initials: G
authors.lastname: Plu-Bureau
authors.forename: Justine
authors.initials: J
authors.lastname: Hugon-Rodin
authors.forename: Véronique
authors.initials: V
authors.lastname: Picard
authors.forename: Marie-Helene
authors.initials: MH
authors.lastname: Horellou
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000990:Antithrombin III / Q000235:genetics*; D001158:Arteries / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D015995:Prevalence; D011379:Prognosis; D012189:Retrospective Studies; D012306:Risk; D013927:Thrombosis / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D054556:Venous Thromboembolism / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D055815:Young Adult
chemical_list: C542513:SERPINC1 protein, human; D000990:Antithrombin III
keywords: Coagulation inhibitor; SERPINC1; antithrombin; thrombophilia; thrombosis