title: Functional consequences of the prothrombotic SERPINC1 rs2227589 polymorphism on antithrombin levels.
abstract: Genetic factors involved in the interindividual variability of antithrombin have not been identified. We studied two polymorphisms of the gene coding for antithrombin (SER-PINC1) in 298 Spanish Caucasian blood donors: rs3138521, a DNA length polymorphism located on the promoter region and rs2227589, a SNP located on intron 1 that has been described as a mild thrombotic risk factor. We detected a complete linkage disequilibrium between these polymorphisms (D'=0.999). The rs3138521 polymorphism has no functional consequences. However, the rs2227589 SNP significantly associated with plasma anti-FXa activity and antithrombin levels: carriers of the A allele had slightly but significantly lower anticoagulant activity and levels than GG subjects (97.0+/-7.3% vs. 94.6+/-8.4%; p=0.032; 99.5+/-5.8% vs. 94.8+/-5.6%; p=0.001; respectively). Our results identified a functional effect of the rs2227589 polymorphism not explained by its linkage with the promoter polymorphism that support the moderate thrombotic risk associated with the A allele.
authors.affiliation: Centro Regional de Hemodonación. C/ Ronda de Garay s/n. Murcia 30003. Spain.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Antón
authors.forename: Raúl
authors.initials: R
authors.lastname: Teruel
authors.forename: Javier
authors.initials: J
authors.lastname: Corral
authors.forename: Antonia
authors.initials: A
authors.lastname: Miñano
authors.forename: Irene
authors.initials: I
authors.lastname: Martínez-Martínez
authors.forename: Adriana
authors.initials: A
authors.lastname: Ordóñez
authors.forename: Vicente
authors.initials: V
authors.lastname: Vicente
authors.forename: Beatriz
authors.initials: B
authors.lastname: Sánchez-Vega
mesh_terms: D000328:Adult; D000990:Antithrombin III; D000991:Antithrombins / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D019774:Blood Coagulation Factor Inhibitors / Q000235:genetics; D005260:Female; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015843:Serpins / Q000235:genetics* / Q000502:physiology; D013030:Spain / Q000453:epidemiology; D019851:Thrombophilia / Q000453:epidemiology / Q000235:genetics*
chemical_list: D000991:Antithrombins; D019774:Blood Coagulation Factor Inhibitors; C542513:SERPINC1 protein, human; D015843:Serpins; D000990:Antithrombin III