title: Influence of the F12 -4 C>T polymorphism on hemostatic tests.
abstract: The common F12 -4 C>T polymorphism significantly regulates plasma levels of FXII, the first element of the intrinsic pathway of coagulation. Due to the robust effects that this pathway has on blood coagulation in vitro, the objective of our study was to evaluate the influence of this polymorphism on different hemostatic tests. We studied 46 hemostatic parameters in 566 participants: 280 patients with mucocutaneous bleeding and 286 controls. The F12 -4T allele, associated with reduced levels of FXII (P < 0.001), also significantly delayed the activated partial thromboplastin time (aPTT) expressed as aPTTr (ratio sample plasma/normal pooled plasma). Thus, both patients and controls carrying the T allele had higher aPTTr than C/C homozygous individuals (P < 0.001). Interestingly, 92% of healthy controls who had prolonged aPTTr carried the F12 -4T allele. Moreover, individuals with the F12 -4T allele also had less thrombin generation (assessed by endogenous thrombin potential, thrombin peak and time to achieve the peak of thrombin) using a test with low tissue factor concentration and explicit contact phase activation. Finally, both patients and controls carrying the F12 -4T allele also displayed significantly lower FIXc and FVIIc levels than C/C individuals (P < 0.01). For all associations except for FVIIc, a gene-dosage effect was observed, and homozygous TT individuals had the farthest values. Our study reveals a significant effect of the F12 -4 C>T polymorphism on hemostatic tests widely used in routine clinical practice.
authors.affiliation: Servicio de Hematología y Oncología Médica HU Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia, Murcia, Spain. javier.corral@carm.es
authors.forename: Javier
authors.initials: J
authors.lastname: Corral
authors.forename: Ana I
authors.initials: AI
authors.lastname: Antón
authors.forename: Teresa
authors.initials: T
authors.lastname: Quiroga
authors.forename: Rocio
authors.initials: R
authors.lastname: González-Conejero
authors.forename: Jaime
authors.initials: J
authors.lastname: Pereira
authors.forename: Vanessa
authors.initials: V
authors.lastname: Roldán
authors.forename: Vicente
authors.initials: V
authors.lastname: Vicente
authors.forename: Diego
authors.initials: D
authors.lastname: Mezzano
mesh_terms: D000483:Alleles; D001779:Blood Coagulation Factors / Q000032:analysis; D016022:Case-Control Studies; D005174:Factor XII / Q000032:analysis / Q000235:genetics*; D018628:Gene Dosage; D005838:Genotype; D006470:Hemorrhage / Q000235:genetics; D006487:Hemostasis / Q000235:genetics*; D006801:Humans; D010314:Partial Thromboplastin Time; D020641:Polymorphism, Single Nucleotide / Q000502:physiology*; D013917:Thrombin / Q000096:biosynthesis
chemical_list: D001779:Blood Coagulation Factors; D005174:Factor XII; D013917:Thrombin