title: The factor V (FV) gene ASP79HIS polymorphism modulates FV plasma levels and affects the activated protein C resistance phenotype in presence of the FV Leiden mutation.
abstract: OBJECTIVE
  In carriers of the factor V (FV) Leiden mutation, different trans-acting gene variants (HR2 haplotype and FV Cambridge mutation) affect activated protein C (APC) sensitivity. Among a series of FV gene variants characterized, the Asp79His polymorphism appeared to be a good candidate for the modulation of FV activity.
  
  
  METHODS
  In a group of 150 apparently healthy subjects without the FV Leiden mutation and in 55 apparently healthy subjects with mutation, genotypes of the Asp79His polymorphism and of the HR haplotype were characterized and plasma levels of FV coagulant activity and APC ratios evaluated.
  
  
  RESULTS
  In the group without the FV Leiden mutation, 16 subjects (10.7%) carried the His 79 allele and 15 subjects (10.0%) the HR2 haplotype. Two of them carried both gene variants. As compared to FV activity levels in non-carriers (106.4+18.5%), values were lower in subjects with the His79 allele (95.2+25.2%; p=0.025) and in those with the HR2 haplotype (93.7+16.2%; p =0.007). FV activity levels were further reduced in carriers of both FV gene variants (78.7+3.3%; p =0.009). APC values were similar among individuals carrying different FV genotypes. In the group with the FV Leiden mutation, APC ratios were lower in subjects carrying the His 79 allele (0.63; p =0.008) or the HR2 haplotype (0.63; p =0.026) than in subjects without (0.69) reflecting FV activity values.
  
  
  CONCLUSIONS
  Present data suggest that carriership of the His79 allele modulate plasma levels of FV coagulant activity and, in subjects carrying the FV Leiden mutation, affects APC sensitivity.
authors.affiliation: Unità di Aterosclerosi e Trombosi, IRCCS Casa Sollievo della Sofferenza, viale Cappuccini, San Giovanni Rotondo, 71013 Foggia, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Bossone
authors.forename: Filomena
authors.initials: F
authors.lastname: Cappucci
authors.forename: Giovanna
authors.initials: G
authors.lastname: D'Andrea
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Brancaccio
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cibelli
authors.forename: Luigi
authors.initials: L
authors.lastname: Iannaccone
authors.forename: Elvira
authors.initials: E
authors.lastname: Grandone
authors.forename: Maurizio
authors.initials: M
authors.lastname: Margaglione
mesh_terms: D020016:Activated Protein C Resistance / Q000235:genetics*; D005165:Factor V / Q000032:analysis / Q000235:genetics*; D006801:Humans; D020125:Mutation, Missense; D010641:Phenotype; D011110:Polymorphism, Genetic
chemical_list: C095381:factor V Leiden; D005165:Factor V