Identification of a genetic risk factor for systemic juvenile rheumatoid arthritis in the 5'-flanking region of the TNFα gene and HLA genes

Yukiji Date, Naoko Seki, Shintaro Kamizono, Takafumi Higuchi, Tomoshige Hirata, Koichiro Miyata, Masahiko Ohkuni, Osamu Tatsuzawa, Shumpei Yokota, Kunitaka Joo, Kohji Ueda, Takehiko Sasazuki, Akinori Kimura, Kyogo Itoh, Hirohisa Kato

Research output: Contribution to journalArticle

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Abstract

Objective. To study polymorphisms in the 5'-flanking promoter/enhancer region of the tumor necrosis factor α (TNFα) gene and in the coding regions of HLA class I and class II genes, in order to better understand the genetic background of juvenile rheumatoid arthritis (JRA). Methods. One hundred eleven Japanese JRA patients (50 with systemic disease, 29 with pauciarticular disease, and 32 with polyarticular disease) and 575 healthy Japanese subjects were examined for the allele frequencies of the TNFα, HLA- A, and HLA class II (DRB1, DRB3, DRB4, DRB5, DQA1, DQB1, DPA1, and DPB1) genes, by DNA typing using the polymerase chain reaction-sequence-specific oligonucleotide probe method. Results. The frequencies of the polymorphic allele at positions -1,031 (T to C substitution, termed -1,031C), -863 (C to A, termed -863A), and -857 (C to T, termed -857T) of the TNFα gene in patients with systemic JRA, but not in those with polyarticular or pauciarticular JRA, were significantly higher than in the healthy controls. The allele frequencies of DRB1*0405 and DQB1*0401 in systemic JRA, but not in the other JRA types, were significantly higher than in controls. Linkage analysis showed that the presence of both the TNFα -857T allele and DRB1*0405 yielded a significantly increased odds ratio (3.84), while the presence of only 1 of them did not yield a high odds ratio (0.87 and 1.58). Conclusion. The -1,031C/-863A allele and the -857T allele of the TNFα gene, both of which are related to high production of tumor necrosis factor α, are associated with systemic JRA. The -857T allele may enhance the effect of the DRB1*0405/DQB1*0401 haplotype in predisposing to development of systemic JRA.

Original languageEnglish
Pages (from-to)2577-2582
Number of pages6
JournalArthritis and rheumatism
Volume42
Issue number12
DOIs
Publication statusPublished - Dec 1 1999

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5' Flanking Region
Juvenile Arthritis
Tumor Necrosis Factor-alpha
Alleles
Gene Frequency
Genes
Odds Ratio
MHC Class II Genes
Gene Order
HLA-A Antigens
DNA Fingerprinting
Oligonucleotide Probes
Genetic Promoter Regions
Haplotypes
Systemic Juvenile Rheumatoid Arthritis
Healthy Volunteers
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

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

Cite this

Identification of a genetic risk factor for systemic juvenile rheumatoid arthritis in the 5'-flanking region of the TNFα gene and HLA genes. / Date, Yukiji; Seki, Naoko; Kamizono, Shintaro; Higuchi, Takafumi; Hirata, Tomoshige; Miyata, Koichiro; Ohkuni, Masahiko; Tatsuzawa, Osamu; Yokota, Shumpei; Joo, Kunitaka; Ueda, Kohji; Sasazuki, Takehiko; Kimura, Akinori; Itoh, Kyogo; Kato, Hirohisa.

In: Arthritis and rheumatism, Vol. 42, No. 12, 01.12.1999, p. 2577-2582.

Research output: Contribution to journalArticle

Date, Y, Seki, N, Kamizono, S, Higuchi, T, Hirata, T, Miyata, K, Ohkuni, M, Tatsuzawa, O, Yokota, S, Joo, K, Ueda, K, Sasazuki, T, Kimura, A, Itoh, K & Kato, H 1999, 'Identification of a genetic risk factor for systemic juvenile rheumatoid arthritis in the 5'-flanking region of the TNFα gene and HLA genes', Arthritis and rheumatism, vol. 42, no. 12, pp. 2577-2582. https://doi.org/10.1002/1529-0131(199912)42:12<2577::AID-ANR10>3.0.CO;2-O
Date, Yukiji ; Seki, Naoko ; Kamizono, Shintaro ; Higuchi, Takafumi ; Hirata, Tomoshige ; Miyata, Koichiro ; Ohkuni, Masahiko ; Tatsuzawa, Osamu ; Yokota, Shumpei ; Joo, Kunitaka ; Ueda, Kohji ; Sasazuki, Takehiko ; Kimura, Akinori ; Itoh, Kyogo ; Kato, Hirohisa. / Identification of a genetic risk factor for systemic juvenile rheumatoid arthritis in the 5'-flanking region of the TNFα gene and HLA genes. In: Arthritis and rheumatism. 1999 ; Vol. 42, No. 12. pp. 2577-2582.
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T1 - Identification of a genetic risk factor for systemic juvenile rheumatoid arthritis in the 5'-flanking region of the TNFα gene and HLA genes

AU - Date, Yukiji

AU - Seki, Naoko

AU - Kamizono, Shintaro

AU - Higuchi, Takafumi

AU - Hirata, Tomoshige

AU - Miyata, Koichiro

AU - Ohkuni, Masahiko

AU - Tatsuzawa, Osamu

AU - Yokota, Shumpei

AU - Joo, Kunitaka

AU - Ueda, Kohji

AU - Sasazuki, Takehiko

AU - Kimura, Akinori

AU - Itoh, Kyogo

AU - Kato, Hirohisa

PY - 1999/12/1

Y1 - 1999/12/1

N2 - Objective. To study polymorphisms in the 5'-flanking promoter/enhancer region of the tumor necrosis factor α (TNFα) gene and in the coding regions of HLA class I and class II genes, in order to better understand the genetic background of juvenile rheumatoid arthritis (JRA). Methods. One hundred eleven Japanese JRA patients (50 with systemic disease, 29 with pauciarticular disease, and 32 with polyarticular disease) and 575 healthy Japanese subjects were examined for the allele frequencies of the TNFα, HLA- A, and HLA class II (DRB1, DRB3, DRB4, DRB5, DQA1, DQB1, DPA1, and DPB1) genes, by DNA typing using the polymerase chain reaction-sequence-specific oligonucleotide probe method. Results. The frequencies of the polymorphic allele at positions -1,031 (T to C substitution, termed -1,031C), -863 (C to A, termed -863A), and -857 (C to T, termed -857T) of the TNFα gene in patients with systemic JRA, but not in those with polyarticular or pauciarticular JRA, were significantly higher than in the healthy controls. The allele frequencies of DRB1*0405 and DQB1*0401 in systemic JRA, but not in the other JRA types, were significantly higher than in controls. Linkage analysis showed that the presence of both the TNFα -857T allele and DRB1*0405 yielded a significantly increased odds ratio (3.84), while the presence of only 1 of them did not yield a high odds ratio (0.87 and 1.58). Conclusion. The -1,031C/-863A allele and the -857T allele of the TNFα gene, both of which are related to high production of tumor necrosis factor α, are associated with systemic JRA. The -857T allele may enhance the effect of the DRB1*0405/DQB1*0401 haplotype in predisposing to development of systemic JRA.

AB - Objective. To study polymorphisms in the 5'-flanking promoter/enhancer region of the tumor necrosis factor α (TNFα) gene and in the coding regions of HLA class I and class II genes, in order to better understand the genetic background of juvenile rheumatoid arthritis (JRA). Methods. One hundred eleven Japanese JRA patients (50 with systemic disease, 29 with pauciarticular disease, and 32 with polyarticular disease) and 575 healthy Japanese subjects were examined for the allele frequencies of the TNFα, HLA- A, and HLA class II (DRB1, DRB3, DRB4, DRB5, DQA1, DQB1, DPA1, and DPB1) genes, by DNA typing using the polymerase chain reaction-sequence-specific oligonucleotide probe method. Results. The frequencies of the polymorphic allele at positions -1,031 (T to C substitution, termed -1,031C), -863 (C to A, termed -863A), and -857 (C to T, termed -857T) of the TNFα gene in patients with systemic JRA, but not in those with polyarticular or pauciarticular JRA, were significantly higher than in the healthy controls. The allele frequencies of DRB1*0405 and DQB1*0401 in systemic JRA, but not in the other JRA types, were significantly higher than in controls. Linkage analysis showed that the presence of both the TNFα -857T allele and DRB1*0405 yielded a significantly increased odds ratio (3.84), while the presence of only 1 of them did not yield a high odds ratio (0.87 and 1.58). Conclusion. The -1,031C/-863A allele and the -857T allele of the TNFα gene, both of which are related to high production of tumor necrosis factor α, are associated with systemic JRA. The -857T allele may enhance the effect of the DRB1*0405/DQB1*0401 haplotype in predisposing to development of systemic JRA.

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