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J Gastroenterol ; 46(5): 676-86, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21116829

RESUMO

BACKGROUND: Accumulating evidence indicates that multiple genetic factors are involved in the pathogenesis of primary biliary cirrhosis (PBC). The aim of this study was to investigate whether polymorphisms of the integrin αV subunit gene (ITGAV), a component of integrin αVß6, which plays an important role in the process of fibrosis, are associated with susceptibility to the onset and/or progression of PBC. METHODS: In the primary study, eight tag single nucleotide polymorphisms (SNPs) in ITGAV were analyzed by polymerase chain reaction (PCR)-restriction fragment length polymorphism, direct DNA sequencing, or high-resolution melting curve analysis in 309 Japanese patients with PBC who were registered in the National Hospital Organization Study Group for Liver Disease in Japan (PBC cohort I) and 293 gender-matched healthy Japanese volunteers (control subjects). For the replication study, 35 PBC patients who progressed to end-stage hepatic failure and underwent liver transplantation (PBC cohort II) were also analyzed. RESULTS: Three tag SNPs (rs3911238, rs10174098, and rs1448427) in ITGAV were significantly associated with the severe progression of PBC, but not with susceptibility to the onset of PBC, in the primary study (PBC cohort I). Among these SNPs, rs1448427 was also significantly associated with the severe progression to end-stage hepatic failure in the replication study of PBC patients who underwent liver transplantation (PBC cohort II). CONCLUSIONS: ITGAV is a genetic determinant for the severe progression of PBC in Japanese patients. Genetic polymorphisms of ITGAV may be useful for identifying high-risk Japanese PBC patients, including those who will require liver transplantation, at the time of initial diagnosis.


Assuntos
Doença Hepática Terminal/etiologia , Integrina alfaV/genética , Cirrose Hepática Biliar/genética , Adulto , Idoso , Povo Asiático/genética , Estudos de Casos e Controles , Progressão da Doença , Doença Hepática Terminal/genética , Doença Hepática Terminal/terapia , Feminino , Predisposição Genética para Doença , Humanos , Japão , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA
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