title: Polymorphisms and mutations in vWF and ADAMTS13 genes and their correlation with plasma levels of FVIII and vWF in patients with deep venous thrombosis.
abstract: BACKGROUND
  Increased levels of factor VIII (FVIII) are a prevalent and independent risk factor for deep venous thrombosis (DVT) and are affected by von Willebrand factor (vWF) levels.
  
  
  METHODS
  ADAMTS13 contributes to vWF levels, and we investigated genetic polymorphisms previously described to be associated with decreased levels of these proteins in 435 patients with DVT (126 M and 309 F; median age 37 years, range 18-68 years) and 580 controls (163 M and 417 F; median age 35 years, range 18-68 years). Subsequently, we investigated the relationship between the genotypes and plasma levels of FVIII, vWF, and DVT risk.
  
  
  RESULTS
  Patients with DVT showed higher plasma levels of FVIII:C, FVIII:Ag, and vWF:Ag (P < .001) when compared to controls. Patients and controls heterozygous for the 4751A>G polymorphism in the vWF gene presented decreased levels of vWF:Ag, FVIII:Ag, and FVIII:C (P < .001), but this was not a protective factor for DVT. Individuals heterozygous for 1852C>G polymorphism in ADAMTS13 gene, which is associated with reduced levels of ADAMTS13, had significantly elevated levels of vWF:Ag (P = .001), FVIII:Ag (P = .01), and FVIII:C (P = .02). However, this polymorphism was not a risk factor for DVT in our study. Heterozygosis for a new polymorphism identified in ADAMTS13 gene, 1787-26G>A, was significantly associated with elevated levels of FVIII:C (P = .02) when compared to wild type.
  
  
  CONCLUSIONS
  Despite the tempting assumption that genetic factors that change ADAMTS13 activity might modulate the risk of DVT by altering vWF and FVIII levels, the polymorphisms analyzed in this study did not correlate with DVT risk among patients investigated.
authors.affiliation: Molecular Biology and Hemostasis Laboratory, Hematology and Hemotherapy Center, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, Brazil. lfbsckayer@hotmail.com
authors.forename: Luis Fernando
authors.initials: LF
authors.lastname: Bittar
authors.forename: Erich Vinícius
authors.initials: EV
authors.lastname: de Paula
authors.forename: Tayana B T
authors.initials: TB
authors.lastname: Mello
authors.forename: Lúcia H
authors.initials: LH
authors.lastname: Siqueira
authors.forename: Fernanda L A
authors.initials: FL
authors.lastname: Orsi
authors.forename: Joyce M
authors.initials: JM
authors.lastname: Annichino-Bizzacchi
mesh_terms: D051722:ADAM Proteins / Q000097:blood / Q000235:genetics; D000071120:ADAMTS13 Protein; D000293:Adolescent; D000328:Adult; D000368:Aged; D005169:Factor VIII / Q000235:genetics / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D012307:Risk Factors; D020246:Venous Thrombosis / Q000097:blood / Q000235:genetics; D014841:von Willebrand Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D014841:von Willebrand Factor; C078147:F8 protein, human; D005169:Factor VIII; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human