Functional consequences of the prothrombotic SERPINC1 rs2227589 polymorphism on antithrombin levels.
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.
Antón
Ana I
AI
Centro Regional de Hemodonación. C/ Ronda de Garay s/n. Murcia 30003. Spain.
Teruel
Raúl
R
Corral
Javier
J
Miñano
Antonia
A
Martínez-Martínez
Irene
I
Ordóñez
Adriana
A
Vicente
Vicente
V
Sánchez-Vega
Beatriz
B
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*
D000991:Antithrombins; D019774:Blood Coagulation Factor Inhibitors; C542513:SERPINC1 protein, human; D015843:Serpins; D000990:Antithrombin III