Study of 18 functional hemostatic polymorphisms in mucocutaneous bleeding disorders.
Hereditary disorders of primary hemostasis, characterized by mucocutaneous bleeding (MCB), are highly prevalent in children. Few cases are clearly monogenic, but the overwhelming majority are classified as mild bleeding disorders, with wide clinical and laboratory heterogeneity suggestive of complex polygenic diseases. In this framework, and by homology with venous thrombosis, some functional polymorphisms affecting the hemostatic system should be considered. We evaluated the role of 18 common hemostatic polymorphisms on the occurrence and severity of MCB in a case-control study including 269 patients and 286 matched controls consecutively recruited. FV Leiden was associated with milder bleeding severity, assessed by a standardized bleeding score (p = 0.013). Multivariate analysis revealed that three additional polymorphisms protected against MCB (F13 Leu34, OR = 0.66; 95% CI, 0.47-0.94; p = 0.024; VKORC1 1173T, OR = 0.59; 95% CI, 0.40-0.87; p = 0.009; and non-O blood group alleles, OR = 0.59; 95% CI, 0.41-0.86; p = 0.006). When combined, these polymorphisms showed an additive protection (OR = 0.24; 95% CI, 0.11-0.52), supporting the polygenic nature of MCB. Our data suggest that some common polymorphisms affecting hemostasis-related genes could protect from bleeding.
Centro Regional de Hemodonación, University of Murcia, Ronda de Garay s/n, Murcia, Spain.
Ana I
AI
Antón
Rocio
R
González-Conejero
Vanessa
V
Roldán
Teresa
T
Quiroga
Beatriz
B
Sánchez-Vega
Javier
J
Corral
Vicente
V
Vicente
Diego
D
Mezzano
D000293:Adolescent; D000328:Adult; D000818:Animals; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005165:Factor V / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006474:Hemorrhagic Disorders / Q000235:genetics*; D006487:Hemostasis / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D009092:Mucous Membrane / Q000503:physiopathology*; D011110:Polymorphism, Genetic; D055815:Young Adult
C095381:factor V Leiden; D005165:Factor V