Functional consequences of the prothrombotic SERPINC1 rs2227589 polymorphism on antithrombin levels

Servicio de Hematología y Oncología Médica H.U. Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia, Spain Correspondence: Javier Corral, Centro Regional de Hemodonación. C/ Ronda de Garay s/n. Murcia 30003. Spain. E-mail: javier.corral{at}carm.es 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. Key words: antithrombin, polymorphism, thrombotic risk.