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R255h Amino acid substitution of protein Z identified in patients with factor V Leiden mutation
Author(s) -
KemkesMatthes Bettina,
Matthes Karl J.,
Souri Masayoshi,
KosekiKuno Shiori,
Ichinose Akitada
Publication year - 2005
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2004.05297.x
Subject(s) - factor v leiden , mutation , protein c , medicine , factor v , gene mutation , gene , thrombophilia , protein s , protein c deficiency , gastroenterology , genetics , biology , thrombosis , venous thrombosis
Summary 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.