Clinical Rheumatology

, Volume 26, Issue 12, pp 2137–2141

Associations between HLA-DRB1, RANK, RANKL, OPG, and IL-17 genotypes and disease severity phenotypes in Japanese patients with early rheumatoid arthritis

Authors

    • Institute of RheumatologyTokyo Women’s Medical University
  • Masayuki Hakoda
    • Department of Nutritional Sciences, Faculty of Human EcologyYasuda Women’s University
  • Naomi Ichikawa
    • Institute of RheumatologyTokyo Women’s Medical University
  • Kenshi Higami
    • Higami Hospital
  • Yuki Nanke
    • Institute of RheumatologyTokyo Women’s Medical University
  • Toru Yago
    • Institute of RheumatologyTokyo Women’s Medical University
  • Naoyuki Kamatani
    • Institute of RheumatologyTokyo Women’s Medical University
  • Shigeru Kotake
    • Institute of RheumatologyTokyo Women’s Medical University
Brief Report

DOI: 10.1007/s10067-007-0745-4

Cite this article as:
Furuya, T., Hakoda, M., Ichikawa, N. et al. Clin Rheumatol (2007) 26: 2137. doi:10.1007/s10067-007-0745-4

Abstract

We examined associations between human leukocyte antigen DRB1 (HLA-DRB1) shared epitope (SE), receptor activator of nuclear factor-kappaB (RANK), RANK ligand (RANKL), osteoprotegerin (OPG), and interleukin 17 (IL-17) genotypes with age of disease onset and radiographic progression in Japanese patients with early rheumatoid arthritis (RA). HLA-DRB1 genotypes were evaluated in 123 patients with early RA (98 female, 25 male) within 1 year of symptom onset. In 72 patients, radiographic progression over a 2-year period was evaluated using Larsen’s methods, and genotypes of three polymorphic sites in RANK, five sites in RANKL, two sites in OPG, and three sites in IL-17 were determined by direct polymerase chain reaction sequencing. Possession of an SE allele was significantly associated with earlier disease onset in females (median 46.9 vs 51.9 years in SE− patients; P = 0.04). Single nucleotide polymorphisms (SNPs) in RANKL (rs2277438, P = 0.028) and IL-17 (rs3804513, P = 0.049) were significantly associated with radiographic progression at 2 years. RANKL-G−, SE− patients (n = 12) had significantly less joint damage than did RANKL-G+, SE− patients (n = 11; P = 0.0038), RANKL-G−, SE+ patients (n = 21; P = 0.0018) and RANKL-G+, SE+ patients (n = 28; P = 0.0024). In Japanese RA patients, HLA-DRB1 SE alleles are associated with disease onset at an earlier age, as has been observed in Caucasian RA patients. In addition, SNPs in RANKL and IL-17 may be associated with radiographic progression in Japanese patients with early RA.

Keywords

IL-17JapaneseRANKLRheumatoid arthritisShared epitopeSingle nucleotide polymorphism

Copyright information

© Clinical Rheumatology 2007