title: Genetic polymorphisms in CTLA4 and SLC4A2 are differentially associated with the pathogenesis of primary biliary cirrhosis in Japanese patients.
abstract: BACKGROUND
  Anti-gp210 and anti-centromere antibodies are different risk factors for the progression of primary biliary cirrhosis (PBC). In order to dissect the genetic basis for the production of these autoantibodies, as well as the development and progression of PBC in Japanese patients, we examined single nucleotide polymorphisms (SNPs) in cytotoxic T-lymphocyte antigen 4 (CTLA4) and solute carrier family 4 anion exchanger, member 2 (SLC4A2), which have been associated with the pathogenesis of PBC in Caucasian patients.
  
  
  METHODS
  Four SNPs for both CTLA4 and SLC4A2 were genotyped, using the polymerase chain reaction-restriction fragment length polymorphism method and TaqMan assay, in 450 Japanese PBC patients and 371 sex-matched healthy controls.
  
  
  RESULTS
  The CTLA4 rs231775, rs3087243, and rs231725 SNPs were significantly associated with PBC susceptibility. The CTLA4 rs231725 SNP was significantly associated with progression to late-stage disease. The CTLA-4 haplotype 1 (rs231775 G, rs231777 C, rs3087243 G, rs231725 A; GCGA) was a risk factor for PBC susceptibility but a protective factor for PBC progression. Conversely, the CTLA-4 haplotype 2 (ACAG) was a protective and risk factor, respectively, for PBC susceptibility and progression. In addition, the CTLA4 rs231777 SNP and haplotype 3 (ATGG) was significantly associated with anti-gp210 antibody production, while SLC4A2 haplotype 4 (rs2069443 A, rs2303933 G, rs2303937 A, rs2303941 T; AGAT) and haplotype 3 (AAGC) were significantly associated with PBC susceptibility and anti-centromere antibody production, respectively.
  
  
  CONCLUSIONS
  CTLA4 and SLC4A2 genetic polymorphisms are differentially associated with PBC development and progression, as well as anti-gp210 or anti-centromere antibody production, in Japanese PBC patients.
authors: Clinical Research Center, National Hospital Organization Nagasaki Medical Center, 2-1001-1 Kubara, Omura, Nagasaki 856-8562, Japan.
authors: Yoshihiro
authors: Y
authors: Aiba
authors: Minoru
authors: M
authors: Nakamura
authors: Satoru
authors: S
authors: Joshita
authors: Tatsuo
authors: T
authors: Inamine
authors: Atsumasa
authors: A
authors: Komori
authors: Kaname
authors: K
authors: Yoshizawa
authors: Takeji
authors: T
authors: Umemura
authors: Hitomi
authors: H
authors: Horie
authors: Kiyoshi
authors: K
authors: Migita
authors: Hiroshi
authors: H
authors: Yatsuhashi
authors: Makoto
authors: M
authors: Nakamuta
authors: Nobuyoshi
authors: N
authors: Fukushima
authors: Takeo
authors: T
authors: Saoshiro
authors: Shigeki
authors: S
authors: Hayashi
authors: Hiroshi
authors: H
authors: Kouno
authors: Hajime
authors: H
authors: Ota
authors: Toyokichi
authors: T
authors: Muro
authors: Yukio
authors: Y
authors: Watanabe
authors: Yoko
authors: Y
authors: Nakamura
authors: Toshiki
authors: T
authors: Komeda
authors: Masaaki
authors: M
authors: Shimada
authors: Naohiko
authors: N
authors: Masaki
authors: Tatsuji
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authors: Komatsu
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authors: Yagura
authors: Kazuhiro
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authors: Sugi
authors: Michiaki
authors: M
authors: Koga
authors: Kazuhiro
authors: K
authors: Tsukamoto
authors: Eiji
authors: E
authors: Tanaka
authors: Hiromi
authors: H
authors: Ishibashi
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