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Genetic polymorphisms of OCT-1 confer susceptibility to severe progression of primary biliary cirrhosis in Japanese patients.
Ohishi, Yuki; Nakamuta, Makoto; Ishikawa, Naoko; Saitoh, Ohki; Nakamura, Hitomi; Aiba, Yoshihiro; Komori, Atsumasa; Migita, Kiyoshi; Yatsuhashi, Hiroshi; Fukushima, Nobuyoshi; Kohjima, Motoyuki; Yoshimoto, Tsuyoshi; Fukuizumi, Kunitaka; Ishibashi, Makoto; Nishino, Takashi; Shirabe, Ken; Taketomi, Akinobu; Maehara, Yoshihiko; Ishibashi, Hiromi; Nakamura, Minoru.
Afiliación
  • Ohishi Y; Department of Pharmacy, Clinical Research Institute, National Hospital Organization (NHO) Kyushu Medical Center, 1-8-1 Jigyouhama, Fukuoka, 810-8563, Japan.
J Gastroenterol ; 49(2): 332-42, 2014 Feb.
Article en En | MEDLINE | ID: mdl-23612856
BACKGROUND: To identify the genetic factors involved in the pathogenesis of primary biliary cirrhosis (PBC), we focused on the organic cation transporter 1 (OCT1/SLC22A1), which is closely associated with phosphatidylcholine synthesis in hepatocytes. METHODS: We selected four (rs683369, rs2282143, rs622342 and rs1443844) OCT-1 single nucleotide polymorphisms (SNPs), and genotyped these SNPs using the TaqMan probe method in 275 Japanese PBC patients and 194 gender-matched, healthy volunteers as controls. RESULTS: The Chi-square test revealed that the rs683369 variant allele (G) was associated with insusceptibility to PBC development [P = 0.009, odds ratio (OR) 0.60, 95 % confidence interval (CI) 0.40-0.88] in an allele model, and that the rs683369 variant allele (G) was associated with jaundice-type progression in a minor allele dominant genotype model (P = 0.032, OR 3.10, 95 % CI 1.05-9.14). The OCT-1 rs2282143 variant (T) and rs622342 variant (C) were also associated with jaundice-type progression in a minor allele recessive genotype model (P = 0.0002, OR 10.58, 95 % CI 2.36-47.54, and P = 0.006, OR 7.84, 95 % CI 1.39-44.36, respectively). Furthermore, the association of OCT-1 rs683369 and rs622342 with susceptibility to jaundice-type progression was confirmed by a replication study with a distinct set of PBC patients who underwent liver transplantation. CONCLUSIONS: The present study is the first report on the association of OCT-1 genetic polymorphisms with the overall development and jaundice-type progression of PBC.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Predisposición Genética a la Enfermedad / Polimorfismo de Nucleótido Simple / Transportador 1 de Catión Orgánico / Ictericia / Cirrosis Hepática Biliar Tipo de estudio: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged País/Región como asunto: Asia Idioma: En Revista: J Gastroenterol Asunto de la revista: GASTROENTEROLOGIA Año: 2014 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Japón
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Predisposición Genética a la Enfermedad / Polimorfismo de Nucleótido Simple / Transportador 1 de Catión Orgánico / Ictericia / Cirrosis Hepática Biliar Tipo de estudio: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged País/Región como asunto: Asia Idioma: En Revista: J Gastroenterol Asunto de la revista: GASTROENTEROLOGIA Año: 2014 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Japón