title: R255h amino acid substitution of protein Z identified in patients with factor V Leiden mutation.
abstract: The clinical significance of diminished protein Z in plasma is controversial. Studies in mice demonstrated that deficiency of protein Z dramatically increases the prothrombotic tendency of factor V Leiden mutation. This finding was confirmed by initial results in humans, indicating that thromboembolism in factor V Leiden patients with lowered protein Z level occurs earlier than in patients with normal protein Z levels. Consequently, the aim of our present study was to find out whether genetic alterations of protein Z were demonstrated in patients with factor V Leiden mutation and early onset of thromboembolic disease. DNA-sequencing of the protein Z gene was performed in two patients with factor V Leiden mutation, early onset of thromboembolism, and lowered protein Z levels. In both patients, R255H substitution of the protein Z gene was identified. Subsequently, the R255H substitution was also found in 12 of 132 additional patients. Patients presenting with the R255H substitution in addition to factor V Leiden mutation showed thromboembolic events more frequently than factor V Leiden patients without R255H substitution of the protein Z gene. In conclusion, R255H substitution of the protein Z gene seems to influence clinical symptoms of thromboembolism in factor V Leiden patients.
authors.affiliation: Department of Internal Medicine, Justus Liebig University Giessen, Giessen, Germany. bettina.kemkes-matthes@innere.med.uni-giessen.de
authors.forename: Bettina
authors.initials: B
authors.lastname: Kemkes-Matthes
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Matthes
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Souri
authors.forename: Shiori
authors.initials: S
authors.lastname: Koseki-Kuno
authors.forename: Akitada
authors.initials: A
authors.lastname: Ichinose
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D001798:Blood Proteins / Q000032:analysis / Q000235:genetics*; D005165:Factor V; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D017422:Sequence Analysis, DNA; D013923:Thromboembolism / Q000097:blood / Q000235:genetics*
chemical_list: D001798:Blood Proteins; C095381:factor V Leiden; C026080:plasma protein Z; D005165:Factor V