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

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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.

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Acknowledgments

We thank Dr. R. L. Wilder for his critical review of the manuscript and Dr. N. Tsuchiya for his useful suggestions. The study was supported by a grant-in-aid from the Ministry of Education, Culture, Science, and Technology of Japan.

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Authors and Affiliations

  1. Institute of Rheumatology, Tokyo Women’s Medical University, 10-22 Kawada-cho, Shinjuku-ku, Tokyo, 162-0054, Japan

    Takefumi Furuya, Naomi Ichikawa, Yuki Nanke, Toru Yago, Naoyuki Kamatani & Shigeru Kotake

  2. Department of Nutritional Sciences, Faculty of Human Ecology, Yasuda Women’s University, Hiroshima, Japan

    Masayuki Hakoda

  3. Higami Hospital, Kashihara, Japan

    Kenshi Higami

Authors
  1. Takefumi Furuya
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  2. Masayuki Hakoda
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  3. Naomi Ichikawa
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  4. Kenshi Higami
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  5. Yuki Nanke
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  6. Toru Yago
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  7. Naoyuki Kamatani
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  8. Shigeru Kotake
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Correspondence to Takefumi Furuya.

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Furuya, T., Hakoda, M., Ichikawa, N. et al. Associations between HLA-DRB1, RANK, RANKL, OPG, and IL-17 genotypes and disease severity phenotypes in Japanese patients with early rheumatoid arthritis. Clin Rheumatol 26, 2137–2141 (2007). https://doi.org/10.1007/s10067-007-0745-4

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  • DOI: https://doi.org/10.1007/s10067-007-0745-4

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