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Combining effects of polymorphism of tumor necrosis factor α 5′-flanking region and HLA-DRB1 on radiological progression in patients with rheumatoid arthritis

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Modern Rheumatology

Abstract

We examined whether polymorphisms upstream of the TNF-α gene (TNFA) were associated with the radiological progression of rheumatoid arthritis (RA). One hundred and twenty-three patients with early RA (disease duration <1 year) were enrolled in a prospective follow-up study. The laboratory findings (ESR, CRP, and RF) were evaluated every 2 months for 2 years. Radiological progression in hands/wrists and feet was evaluated every 6 months for 2 years using Larsen’s score. HLA-DRB1 genotype was determined by PCR-RFLP method. The genotypes for -1031, -863, and -857 single-nucleotide polymorphisms in the upstream 5′-flanking region of TNFA were determined by a PCR-preferential homoduplex formation assay in patients with RA and 265 healthy controls. Four TNFA alleles (U01, U02, U03, and U04) were identified. The frequency of individuals with U02 was significantly higher in patients than in controls (P = 0.0025). Radiographs of hands/wrists/feet were available for 72 patients after 1 year and for 73 patients after 2 years. When the HLA-DRB1 genotype was analyzed simultaneously, patients possessing U02 without an HLA-DRB1 shared epitope (SE) (U02+SE−) showed the lowest progression of Larsen’s score (12 months). There was no difference in the level of ESR, CRP, or RF at the first visit among U02+SE+, U02+SE−, U02−SE+, and U02−SE− groups. The combination of the polymorphism of the TNFA upstream promoter region and HLA-DRB1 allele was associated with radiological progression in the early stage of RA.

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Acknowledgments

This work was supported by a Grant-in-Aid for Scientific Research (B) from the Ministry of Education, Science, Sports, and Culture of Japan, and a Health and Labor Sciences Research Grant from the Ministry of Health, Labor, and Welfare 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

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

  2. Department of Nutritional Sciences, Faculty of Human Ecology, Yasuda Women’s University, 6-13-1 Ando, Asaminami-ku, Hiroshima, 731-0153, Japan

    Masayuki Hakoda

  3. Higami Hospital, 701 Kuzumoto-cho, Kashihara, Nara, 634-0007, Japan

    Kenshi Higami

  4. Department of Human Genetics, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan

    Katsushi Tokunaga

  5. Doctoral Program in Social and Environmental Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan

    Aya Kawasaki & Naoyuki Tsuchiya

Authors
  1. Naomi Ichikawa
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  2. Shigeru Kotake
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  3. Masayuki Hakoda
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  4. Kenshi Higami
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  5. Aya Kawasaki
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  6. Takefumi Furuya
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  7. Yuki Nanke
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  8. Naoyuki Tsuchiya
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  9. Katsushi Tokunaga
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  10. Naoyuki Kamatani
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Correspondence to Naomi Ichikawa.

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Ichikawa, N., Kotake, S., Hakoda, M. et al. Combining effects of polymorphism of tumor necrosis factor α 5′-flanking region and HLA-DRB1 on radiological progression in patients with rheumatoid arthritis. Mod Rheumatol 19, 134–139 (2009). https://doi.org/10.1007/s10165-008-0134-0

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  • DOI: https://doi.org/10.1007/s10165-008-0134-0

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