Tumor necrosis factor α 5'-flanking region, tumor necrosis factor receptor II, and HLA-DRB1 polymorphisms in Japanese patients with rheumatoid arthritis

Tsukasa Shibue, Naoyuki Tsuchiya, Tae Komata, Masaki Matsushita, Michiko Shiota, Jun Ohashi, Masatoshi Wakui, Kunio Matsuta, Katsushi Tokunaga

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Objective. New polymorphisms affecting transcriptional activity were recently reported within the 5'-flanking region of the tumor necrosis factor α gene (TNFA). In addition, genome-wide linkage screening indicated 1p36 as one of the candidate chromosomal regions where the TNF receptor II gene (TNFR2) is located. In the present study, HLA-DRB1, TNFA promoter, and TNFR2 genotypes were determined to examine whether these polymorphisms are associated with rheumatoid arthritis (RA), either independently or in combination. Methods. Genotypes of HLA-DRB1, TNFA upstream promoter, and TNFR2 codon 196 were determined in 545 Japanese patients with RA and 265 healthy controls. Association of these genes with susceptibility to RA was analyzed both independently and after stratification by one of the genotypes. Results. As expected, the HLA-DRB1 shared epitope was strongly associated with RA. In addition, a significant negative association of DRB1*1405 and 1302 was observed. Furthermore, DRB1*1405 was suggested to possess a protective role for the development of RA in DRB1*0405-positive individuals. A significant increase in TNFA-U02 in RA was detected, which was not independent of DRB1*0405. A significant association was not observed between TNFR2-196M/R polymorphism and RA. Conclusion. Among the 3 genes examined in this study, HLA-DRB1 was considered to be most strongly associated with RA.

Original languageEnglish
Pages (from-to)753-757
Number of pages5
JournalArthritis and Rheumatism
Volume43
Issue number4
DOIs
Publication statusPublished - 2000 Sep 18

    Fingerprint

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

Cite this