Mutations and common polymorphisms in <i>ADAMTS13</i> gene responsible for von Willebrand factor-cleaving protease activity
-
- Koichi Kokame
- Research Institute and Division of Hypertension and Nephrology, National Cardiovascular Center, Suita, Osaka 565-8565, Japan; Departments of Blood Transfusion Medicine and Health Science, Nara Medical University, Kashihara, Nara 634-8522, Japan; First Research Department, Chemo-Sero-Therapeutic Research Institute, Kumamoto 869-1298, Japan; Department of Pediatrics, Yodogawa Christian Hospital, Osaka 533-0032, Japan; and Department of Pediatrics, Sapporo Kosei General Hospital, Sapporo 060-0033, Japan
-
- Masanori Matsumoto
- Research Institute and Division of Hypertension and Nephrology, National Cardiovascular Center, Suita, Osaka 565-8565, Japan; Departments of Blood Transfusion Medicine and Health Science, Nara Medical University, Kashihara, Nara 634-8522, Japan; First Research Department, Chemo-Sero-Therapeutic Research Institute, Kumamoto 869-1298, Japan; Department of Pediatrics, Yodogawa Christian Hospital, Osaka 533-0032, Japan; and Department of Pediatrics, Sapporo Kosei General Hospital, Sapporo 060-0033, Japan
-
- Kenji Soejima
- Research Institute and Division of Hypertension and Nephrology, National Cardiovascular Center, Suita, Osaka 565-8565, Japan; Departments of Blood Transfusion Medicine and Health Science, Nara Medical University, Kashihara, Nara 634-8522, Japan; First Research Department, Chemo-Sero-Therapeutic Research Institute, Kumamoto 869-1298, Japan; Department of Pediatrics, Yodogawa Christian Hospital, Osaka 533-0032, Japan; and Department of Pediatrics, Sapporo Kosei General Hospital, Sapporo 060-0033, Japan
-
- Hideo Yagi
- Research Institute and Division of Hypertension and Nephrology, National Cardiovascular Center, Suita, Osaka 565-8565, Japan; Departments of Blood Transfusion Medicine and Health Science, Nara Medical University, Kashihara, Nara 634-8522, Japan; First Research Department, Chemo-Sero-Therapeutic Research Institute, Kumamoto 869-1298, Japan; Department of Pediatrics, Yodogawa Christian Hospital, Osaka 533-0032, Japan; and Department of Pediatrics, Sapporo Kosei General Hospital, Sapporo 060-0033, Japan
-
- Hiromichi Ishizashi
- Research Institute and Division of Hypertension and Nephrology, National Cardiovascular Center, Suita, Osaka 565-8565, Japan; Departments of Blood Transfusion Medicine and Health Science, Nara Medical University, Kashihara, Nara 634-8522, Japan; First Research Department, Chemo-Sero-Therapeutic Research Institute, Kumamoto 869-1298, Japan; Department of Pediatrics, Yodogawa Christian Hospital, Osaka 533-0032, Japan; and Department of Pediatrics, Sapporo Kosei General Hospital, Sapporo 060-0033, Japan
-
- Masahisa Funato
- Research Institute and Division of Hypertension and Nephrology, National Cardiovascular Center, Suita, Osaka 565-8565, Japan; Departments of Blood Transfusion Medicine and Health Science, Nara Medical University, Kashihara, Nara 634-8522, Japan; First Research Department, Chemo-Sero-Therapeutic Research Institute, Kumamoto 869-1298, Japan; Department of Pediatrics, Yodogawa Christian Hospital, Osaka 533-0032, Japan; and Department of Pediatrics, Sapporo Kosei General Hospital, Sapporo 060-0033, Japan
-
- Hiroshi Tamai
- Research Institute and Division of Hypertension and Nephrology, National Cardiovascular Center, Suita, Osaka 565-8565, Japan; Departments of Blood Transfusion Medicine and Health Science, Nara Medical University, Kashihara, Nara 634-8522, Japan; First Research Department, Chemo-Sero-Therapeutic Research Institute, Kumamoto 869-1298, Japan; Department of Pediatrics, Yodogawa Christian Hospital, Osaka 533-0032, Japan; and Department of Pediatrics, Sapporo Kosei General Hospital, Sapporo 060-0033, Japan
-
- Mutsuko Konno
- Research Institute and Division of Hypertension and Nephrology, National Cardiovascular Center, Suita, Osaka 565-8565, Japan; Departments of Blood Transfusion Medicine and Health Science, Nara Medical University, Kashihara, Nara 634-8522, Japan; First Research Department, Chemo-Sero-Therapeutic Research Institute, Kumamoto 869-1298, Japan; Department of Pediatrics, Yodogawa Christian Hospital, Osaka 533-0032, Japan; and Department of Pediatrics, Sapporo Kosei General Hospital, Sapporo 060-0033, Japan
-
- Kei Kamide
- Research Institute and Division of Hypertension and Nephrology, National Cardiovascular Center, Suita, Osaka 565-8565, Japan; Departments of Blood Transfusion Medicine and Health Science, Nara Medical University, Kashihara, Nara 634-8522, Japan; First Research Department, Chemo-Sero-Therapeutic Research Institute, Kumamoto 869-1298, Japan; Department of Pediatrics, Yodogawa Christian Hospital, Osaka 533-0032, Japan; and Department of Pediatrics, Sapporo Kosei General Hospital, Sapporo 060-0033, Japan
-
- Yuhei Kawano
- Research Institute and Division of Hypertension and Nephrology, National Cardiovascular Center, Suita, Osaka 565-8565, Japan; Departments of Blood Transfusion Medicine and Health Science, Nara Medical University, Kashihara, Nara 634-8522, Japan; First Research Department, Chemo-Sero-Therapeutic Research Institute, Kumamoto 869-1298, Japan; Department of Pediatrics, Yodogawa Christian Hospital, Osaka 533-0032, Japan; and Department of Pediatrics, Sapporo Kosei General Hospital, Sapporo 060-0033, Japan
-
- Toshiyuki Miyata
- Research Institute and Division of Hypertension and Nephrology, National Cardiovascular Center, Suita, Osaka 565-8565, Japan; Departments of Blood Transfusion Medicine and Health Science, Nara Medical University, Kashihara, Nara 634-8522, Japan; First Research Department, Chemo-Sero-Therapeutic Research Institute, Kumamoto 869-1298, Japan; Department of Pediatrics, Yodogawa Christian Hospital, Osaka 533-0032, Japan; and Department of Pediatrics, Sapporo Kosei General Hospital, Sapporo 060-0033, Japan
-
- Yoshihiro Fujimura
- Research Institute and Division of Hypertension and Nephrology, National Cardiovascular Center, Suita, Osaka 565-8565, Japan; Departments of Blood Transfusion Medicine and Health Science, Nara Medical University, Kashihara, Nara 634-8522, Japan; First Research Department, Chemo-Sero-Therapeutic Research Institute, Kumamoto 869-1298, Japan; Department of Pediatrics, Yodogawa Christian Hospital, Osaka 533-0032, Japan; and Department of Pediatrics, Sapporo Kosei General Hospital, Sapporo 060-0033, Japan
抄録
<jats:p> von Willebrand factor (VWF) is synthesized primarily in vascular endothelial cells and secreted into the plasma as unusually large VWF multimers. Normally, these multimers are quickly degraded into smaller forms by a plasma metalloproteinase, VWF-cleaving protease (VWF-CP). Decreases in the activity of this enzyme result in congenital and acquired thrombotic thrombocytopenic purpura (TTP). The human VWF-CP has recently been purified. Cloning of the corresponding cDNA revealed that the 1,427-aa polypeptide is a member of the ADAMTS gene family, termed <jats:italic>ADAMTS13</jats:italic> . Twelve rare mutations in this gene have been identified in patients with congenital TTP. Here, we report missense and nonsense mutations in two Japanese families with Upshaw–Schulman syndrome, congenital TTP with neonatal onset and frequent relapses. The comparison of individual <jats:italic>ADAMTS13</jats:italic> genotypes and plasma VWF-CP activities indicated that the R268P, Q449stop, and C508Y mutations abrogated activity of the enzyme, whereas the P475S mutant retained low but significant activity. The effects of these mutations were further confirmed by expression analysis in HeLa cells. Recombinant VWF-CP containing either the R268P or C508Y mutations was not secreted from cells. In contrast, Q449stop and P475S mutants were normally secreted but demonstrated minimal activity. Genotype analysis of 364 Japanese subjects revealed that P475S is heterozygous in 9.6% of individuals, suggesting that approximately 10% of the Japanese population possesses reduced VWF-CP activity. We report on a single-nucleotide polymorphism associated with alterations in VWF-CP activity; it will be important to assess this single-nucleotide polymorphism as a risk factor for thrombotic disorders. </jats:p>
収録刊行物
-
- Proceedings of the National Academy of Sciences
-
Proceedings of the National Academy of Sciences 99 (18), 11902-11907, 2002-08-14
Proceedings of the National Academy of Sciences
- Tweet
キーワード
詳細情報 詳細情報について
-
- CRID
- 1363388843910675968
-
- NII論文ID
- 80015556277
-
- ISSN
- 10916490
- 00278424
-
- データソース種別
-
- Crossref
- CiNii Articles