title: ADAMTS13 activity and genetic mutations in Japan.
abstract: Thrombotic thrombocytopenic purpura (TTP), a life threatening disease, can be induced by congenital or acquired deficiency of plasma metalloprotease ADAMTS13. Since the publication of the first genetic analysis in patients with congenital ADAMTS13 deficiency in 2001, more than 100 genetic defects in the ADAMTS13 gene have been reported worldwide. Genetic analysis in patients with ADAMTS13 deficiency has greatly contributed to the understanding of the etiology of TTP. A rapid and quantitative assay method for the plasma ADAMTS13 activity was developed recently in 2005 and opened a new area of TTP research - namely genetic research using a general population to evaluate age and gender differences of ADAMTS13 activity as well as phenotype - genotype correlations of genetic polymorphisms and estimation of a homozygote or a compound heterozygote ADAMTS13 deficiencies. The Japanese general population study included 3616 individuals with an age between 30 - 80 years confirming other studies that while ADAMTS13 activity decreased with age, VWF antigen increased and VWF antigen levels are lowest in blood group O indviduals, whereas ADAMTS13 activity levels were not associated with the AB0 blood group. 25 polymorphisms with a minor allele frequency of more than 0.01 were found, among them 6 missense mutations and 19 synonymous mutations, except P475S missense polymorphisms that was only idenitified in an East Asian population, characterized by reduced ADAMTS13 activity. Prevalence of congenital ADAMTS13 deficiency in the Japanese population was estimated about one individual in 1.1 x 106 to be homozygote or compound heterozygote for ADAMTS13 deficiency. So far more than 40 mutations in Japanese congenital TTP patients were found, but R193W, Q449*, C754Afs*24 (c.2259delA) and C908Y were identified in more than four patients suggesting the precipitaion of these mutations in the Japanese population.
authors.affiliation: Department of Molecular Pathogenesis, National Cerebral and Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Japan. miyata@ri.ncvc.go.jp
authors.forename: T
authors.initials: T
authors.lastname: Miyata
authors.forename: K
authors.initials: K
authors.lastname: Kokame
authors.forename: M
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Y
authors.initials: Y
authors.lastname: Fujimura
mesh_terms: D051722:ADAM Proteins / Q000235:genetics*; D000071120:ADAMTS13 Protein; D017677:Age Distribution; D004789:Enzyme Activation / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence; D011697:Purpura, Thrombotic Thrombocytopenic / Q000453:epidemiology* / Q000235:genetics*; D018570:Risk Assessment; D017678:Sex Distribution
chemical_list: D005819:Genetic Markers; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human