Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

Genetic polymorphisms in CTLA4 and SLC4A2 are differentially associated with the pathogenesis of primary biliary cirrhosis in Japanese patients.

Authors: Aiba, Yoshihiro  Nakamura, Minoru  Joshita, Satoru  Inamine, Tatsuo  Komori, Atsumasa  Yoshizawa, Kaname  Umemura, Takeji  Horie, Hitomi  Migita, Kiyoshi  Yatsuhashi, Hiroshi  Nakamuta, Makoto  Fukushima, Nobuyoshi  Saoshiro, Takeo  Hayashi, Shigeki  Kouno, Hiroshi  Ota, Hajime  Muro, Toyokichi  Watanabe, Yukio  Nakamura, Yoko  Komeda, Toshiki  Shimada, Masaaki  Masaki, Naohiko  Komatsu, Tatsuji  Yagura, Michiyasu  Sugi, Kazuhiro  Koga, Michiaki  Tsukamoto, Kazuhiro  Tanaka, Eiji  Ishibashi, Hiromi  PBC Study Group in NHOSLJ,  
Citation: Aiba Y, etal., J Gastroenterol. 2011 Oct;46(10):1203-12. doi: 10.1007/s00535-011-0417-7. Epub 2011 May 19.
Pubmed: (View Article at PubMed) PMID:21594562
DOI: Full-text: DOI:10.1007/s00535-011-0417-7


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.

Annotation

Disease Annotations
Objects Annotated

Additional Information

 
RGD Object Information
RGD ID: 14398743
Created: 2019-04-25
Species: All species
Last Modified: 2019-04-25
Status: ACTIVE



NHLBI Logo

RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.