An association analysis of HLA-DRB1 with systemic lupus erythematosus and rheumatoid arthritis in a Japanese population: Effects of *09:01 allele on disease phenotypes

Kenichi Shimane, Yuta Kochi, Akari Suzuki, Yukinori Okada, Tomonori Ishii, Tetsuya Horita, Kazuyoshi Saito, Akiko Okamoto, Norihiro Nishimoto, Keiko Myouzen, Michiaki Kubo, Michito Hirakata, Takayuki Sumida, Yoshinari Takasaki, Ryo Yamada, Yusuke Nakamura, Naoyuki Kamatani, Kazuhiko Yamamoto

研究成果: Article

33 引用 (Scopus)

抄録

Objective: To re-evaluate the roles of HLA-DRB1 alleles in susceptibility to SLE and RA and their effects on autoantibody status in large-scale Japanese cohorts. Methods: A total of 656 SLE, 2410 RA and 911 control subjects, who were all Japanese, were genotyped for HLA-DRB1 alleles using sequence-specific oligonucleotide probes. The association of alleles with disease susceptibility was tested by logistic regression analysis and by the relative predispositional effect method. The association with autoantibody status was examined by the standard -2 test. Results: HLA-DRB1*15:01, *09:01, *08:02 and *04:01 were significantly associated with SLE susceptibility, while shared epitope (SE) alleles and DRB1*09:01 were associated with RA susceptibility. The compound heterozygote of DRB1*09:01/*15:01 conferred an increased risk for SLE compared with the homozygotes for DRB1*09:01 and *15:01 and was associated with earlier onset of disease, whereas the compound effect of DRB1-SE/*09:01 was not clear in RA. DRB1*09:01 was significantly associated with the appearance of anti-Sm antibody in SLE as well as ACPA in RA, while protectively associated with anti-dsDNA antibody in SLE. No significant interaction was observed between DRB1*09:01 and smoking status for the appearance of ACPA, unlike that observed in SE alleles in RA. Conclusion: We identified HLA-DRB1 alleles associated with SLE and RA in a Japanese population and demonstrated a shared susceptibility of DRB1*09:01 between the diseases as well as its effect on autoantibody production.

元の言語English
ページ(範囲)1172-1182
ページ数11
ジャーナルRheumatology (United Kingdom)
52
発行部数7
DOI
出版物ステータスPublished - 2013 7

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HLA-DRB1 Chains
Systemic Lupus Erythematosus
Rheumatoid Arthritis
Alleles
Phenotype
Autoantibodies
Population
Epitopes
Anti-Idiotypic Antibodies
Oligonucleotide Probes
Disease Susceptibility
Homozygote
Heterozygote
Logistic Models
Smoking
Regression Analysis

ASJC Scopus subject areas

  • Rheumatology
  • Pharmacology (medical)

これを引用

An association analysis of HLA-DRB1 with systemic lupus erythematosus and rheumatoid arthritis in a Japanese population : Effects of *09:01 allele on disease phenotypes. / Shimane, Kenichi; Kochi, Yuta; Suzuki, Akari; Okada, Yukinori; Ishii, Tomonori; Horita, Tetsuya; Saito, Kazuyoshi; Okamoto, Akiko; Nishimoto, Norihiro; Myouzen, Keiko; Kubo, Michiaki; Hirakata, Michito; Sumida, Takayuki; Takasaki, Yoshinari; Yamada, Ryo; Nakamura, Yusuke; Kamatani, Naoyuki; Yamamoto, Kazuhiko.

:: Rheumatology (United Kingdom), 巻 52, 番号 7, 07.2013, p. 1172-1182.

研究成果: Article

Shimane, K, Kochi, Y, Suzuki, A, Okada, Y, Ishii, T, Horita, T, Saito, K, Okamoto, A, Nishimoto, N, Myouzen, K, Kubo, M, Hirakata, M, Sumida, T, Takasaki, Y, Yamada, R, Nakamura, Y, Kamatani, N & Yamamoto, K 2013, 'An association analysis of HLA-DRB1 with systemic lupus erythematosus and rheumatoid arthritis in a Japanese population: Effects of *09:01 allele on disease phenotypes', Rheumatology (United Kingdom), 巻. 52, 番号 7, pp. 1172-1182. https://doi.org/10.1093/rheumatology/kes427
Shimane, Kenichi ; Kochi, Yuta ; Suzuki, Akari ; Okada, Yukinori ; Ishii, Tomonori ; Horita, Tetsuya ; Saito, Kazuyoshi ; Okamoto, Akiko ; Nishimoto, Norihiro ; Myouzen, Keiko ; Kubo, Michiaki ; Hirakata, Michito ; Sumida, Takayuki ; Takasaki, Yoshinari ; Yamada, Ryo ; Nakamura, Yusuke ; Kamatani, Naoyuki ; Yamamoto, Kazuhiko. / An association analysis of HLA-DRB1 with systemic lupus erythematosus and rheumatoid arthritis in a Japanese population : Effects of *09:01 allele on disease phenotypes. :: Rheumatology (United Kingdom). 2013 ; 巻 52, 番号 7. pp. 1172-1182.
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title = "An association analysis of HLA-DRB1 with systemic lupus erythematosus and rheumatoid arthritis in a Japanese population: Effects of *09:01 allele on disease phenotypes",
abstract = "Objective: To re-evaluate the roles of HLA-DRB1 alleles in susceptibility to SLE and RA and their effects on autoantibody status in large-scale Japanese cohorts. Methods: A total of 656 SLE, 2410 RA and 911 control subjects, who were all Japanese, were genotyped for HLA-DRB1 alleles using sequence-specific oligonucleotide probes. The association of alleles with disease susceptibility was tested by logistic regression analysis and by the relative predispositional effect method. The association with autoantibody status was examined by the standard -2 test. Results: HLA-DRB1*15:01, *09:01, *08:02 and *04:01 were significantly associated with SLE susceptibility, while shared epitope (SE) alleles and DRB1*09:01 were associated with RA susceptibility. The compound heterozygote of DRB1*09:01/*15:01 conferred an increased risk for SLE compared with the homozygotes for DRB1*09:01 and *15:01 and was associated with earlier onset of disease, whereas the compound effect of DRB1-SE/*09:01 was not clear in RA. DRB1*09:01 was significantly associated with the appearance of anti-Sm antibody in SLE as well as ACPA in RA, while protectively associated with anti-dsDNA antibody in SLE. No significant interaction was observed between DRB1*09:01 and smoking status for the appearance of ACPA, unlike that observed in SE alleles in RA. Conclusion: We identified HLA-DRB1 alleles associated with SLE and RA in a Japanese population and demonstrated a shared susceptibility of DRB1*09:01 between the diseases as well as its effect on autoantibody production.",
keywords = "Asian population, Association study, Autoantibody, Genetics, Human leukocyte antigen DRB1, Rheumatoid arthritis, Systemic lupus erythematosus",
author = "Kenichi Shimane and Yuta Kochi and Akari Suzuki and Yukinori Okada and Tomonori Ishii and Tetsuya Horita and Kazuyoshi Saito and Akiko Okamoto and Norihiro Nishimoto and Keiko Myouzen and Michiaki Kubo and Michito Hirakata and Takayuki Sumida and Yoshinari Takasaki and Ryo Yamada and Yusuke Nakamura and Naoyuki Kamatani and Kazuhiko Yamamoto",
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pages = "1172--1182",
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TY - JOUR

T1 - An association analysis of HLA-DRB1 with systemic lupus erythematosus and rheumatoid arthritis in a Japanese population

T2 - Effects of *09:01 allele on disease phenotypes

AU - Shimane, Kenichi

AU - Kochi, Yuta

AU - Suzuki, Akari

AU - Okada, Yukinori

AU - Ishii, Tomonori

AU - Horita, Tetsuya

AU - Saito, Kazuyoshi

AU - Okamoto, Akiko

AU - Nishimoto, Norihiro

AU - Myouzen, Keiko

AU - Kubo, Michiaki

AU - Hirakata, Michito

AU - Sumida, Takayuki

AU - Takasaki, Yoshinari

AU - Yamada, Ryo

AU - Nakamura, Yusuke

AU - Kamatani, Naoyuki

AU - Yamamoto, Kazuhiko

PY - 2013/7

Y1 - 2013/7

N2 - Objective: To re-evaluate the roles of HLA-DRB1 alleles in susceptibility to SLE and RA and their effects on autoantibody status in large-scale Japanese cohorts. Methods: A total of 656 SLE, 2410 RA and 911 control subjects, who were all Japanese, were genotyped for HLA-DRB1 alleles using sequence-specific oligonucleotide probes. The association of alleles with disease susceptibility was tested by logistic regression analysis and by the relative predispositional effect method. The association with autoantibody status was examined by the standard -2 test. Results: HLA-DRB1*15:01, *09:01, *08:02 and *04:01 were significantly associated with SLE susceptibility, while shared epitope (SE) alleles and DRB1*09:01 were associated with RA susceptibility. The compound heterozygote of DRB1*09:01/*15:01 conferred an increased risk for SLE compared with the homozygotes for DRB1*09:01 and *15:01 and was associated with earlier onset of disease, whereas the compound effect of DRB1-SE/*09:01 was not clear in RA. DRB1*09:01 was significantly associated with the appearance of anti-Sm antibody in SLE as well as ACPA in RA, while protectively associated with anti-dsDNA antibody in SLE. No significant interaction was observed between DRB1*09:01 and smoking status for the appearance of ACPA, unlike that observed in SE alleles in RA. Conclusion: We identified HLA-DRB1 alleles associated with SLE and RA in a Japanese population and demonstrated a shared susceptibility of DRB1*09:01 between the diseases as well as its effect on autoantibody production.

AB - Objective: To re-evaluate the roles of HLA-DRB1 alleles in susceptibility to SLE and RA and their effects on autoantibody status in large-scale Japanese cohorts. Methods: A total of 656 SLE, 2410 RA and 911 control subjects, who were all Japanese, were genotyped for HLA-DRB1 alleles using sequence-specific oligonucleotide probes. The association of alleles with disease susceptibility was tested by logistic regression analysis and by the relative predispositional effect method. The association with autoantibody status was examined by the standard -2 test. Results: HLA-DRB1*15:01, *09:01, *08:02 and *04:01 were significantly associated with SLE susceptibility, while shared epitope (SE) alleles and DRB1*09:01 were associated with RA susceptibility. The compound heterozygote of DRB1*09:01/*15:01 conferred an increased risk for SLE compared with the homozygotes for DRB1*09:01 and *15:01 and was associated with earlier onset of disease, whereas the compound effect of DRB1-SE/*09:01 was not clear in RA. DRB1*09:01 was significantly associated with the appearance of anti-Sm antibody in SLE as well as ACPA in RA, while protectively associated with anti-dsDNA antibody in SLE. No significant interaction was observed between DRB1*09:01 and smoking status for the appearance of ACPA, unlike that observed in SE alleles in RA. Conclusion: We identified HLA-DRB1 alleles associated with SLE and RA in a Japanese population and demonstrated a shared susceptibility of DRB1*09:01 between the diseases as well as its effect on autoantibody production.

KW - Asian population

KW - Association study

KW - Autoantibody

KW - Genetics

KW - Human leukocyte antigen DRB1

KW - Rheumatoid arthritis

KW - Systemic lupus erythematosus

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