Increased susceptibility to rheumatoid arthritis in koreans heterozygous for HLA-DRB1*0405 and *0901

Hye Soon Lee, Kyung Wha Lee, Gwan Gyu Song, Hyun Ah Kim, Shin Yoon Kim, Sang Cheol Bae

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

Objective. To investigate the association of susceptibility and protective HLA-DRB1 alleles with rheumatoid arthritis (RA) and its clinical markers in an Asian population. Methods. All RA patients (n = 574) and control subjects (n = 392) were Korean. HLA-DRB1 typing and further subtyping of all alleles was performed by polymerase chain reaction, sequence-specific oligonucleotide probe hybridization, and direct DNA sequencing analysis. We used a relative predispositional effects (RPEs) method and a false discovery rate correction method for multiple comparisons. Results. The DRB1*0405 and *0901 alleles showed the most significant associations with RA (P = 7.83 × 1024, odds ratio [OR] 4.40 [95% confidence interval (95% CI) 3.24-5.99], and P = 3.76 × 10-9, OR 2.47 [95% CI 1.82-3.36], respectively). The RPEs test showed that the DRB1*0401 and *0410 alleles conferred susceptibility and that the DRB1*0701, *0802, *1301, *1302, *1403, and *1405 alleles showed significant protective effects. Susceptibility and protective alleles both showed a pattern consistent with additive genetic effects, and each influenced RA independently of the other. The compound heterozygote DRB1*0405/ *0901 was associated with the highest risk of RA (corrected P = 1.81 × 10-11, OR 58.2 [95% CI 7.95-425.70]). The mean age at disease onset was ∼4 years earlier or was 3 years earlier, respectively, in patients with at least 1 copy of the DRB1*0405 or the DRB1*0901 allele. Radiographic changes (stages II-IV) were more frequent in patients with at least 1 copy of DRB1*0405 (P = 0.032, 92.6% versus §4.3%, OR 2.33 [95% CI 1.24-4.39]). Conclusion. The DRB1*0405/*0901 heterozygote has the strongest association with RA, suggesting that this heterozygote enhances the susceptibility to RA in Koreans.

Original languageEnglish
Pages (from-to)3468-3475
Number of pages8
JournalArthritis and Rheumatism
Volume50
Issue number11
DOIs
Publication statusPublished - 2004 Nov 1

Fingerprint

Rheumatoid Arthritis
Alleles
Heterozygote
Odds Ratio
Confidence Intervals
HLA-DRB1 Chains
Histocompatibility Testing
Oligonucleotide Probes
HLA-DRB1*04:05 antigen
DNA Sequence Analysis
Age of Onset
Biomarkers
Polymerase Chain Reaction
Population

ASJC Scopus subject areas

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

Cite this

Increased susceptibility to rheumatoid arthritis in koreans heterozygous for HLA-DRB1*0405 and *0901. / Lee, Hye Soon; Lee, Kyung Wha; Song, Gwan Gyu; Kim, Hyun Ah; Kim, Shin Yoon; Bae, Sang Cheol.

In: Arthritis and Rheumatism, Vol. 50, No. 11, 01.11.2004, p. 3468-3475.

Research output: Contribution to journalArticle

Lee, Hye Soon ; Lee, Kyung Wha ; Song, Gwan Gyu ; Kim, Hyun Ah ; Kim, Shin Yoon ; Bae, Sang Cheol. / Increased susceptibility to rheumatoid arthritis in koreans heterozygous for HLA-DRB1*0405 and *0901. In: Arthritis and Rheumatism. 2004 ; Vol. 50, No. 11. pp. 3468-3475.
@article{a442392e17034380b6477ab34d82aedf,
title = "Increased susceptibility to rheumatoid arthritis in koreans heterozygous for HLA-DRB1*0405 and *0901",
abstract = "Objective. To investigate the association of susceptibility and protective HLA-DRB1 alleles with rheumatoid arthritis (RA) and its clinical markers in an Asian population. Methods. All RA patients (n = 574) and control subjects (n = 392) were Korean. HLA-DRB1 typing and further subtyping of all alleles was performed by polymerase chain reaction, sequence-specific oligonucleotide probe hybridization, and direct DNA sequencing analysis. We used a relative predispositional effects (RPEs) method and a false discovery rate correction method for multiple comparisons. Results. The DRB1*0405 and *0901 alleles showed the most significant associations with RA (P = 7.83 × 1024, odds ratio [OR] 4.40 [95{\%} confidence interval (95{\%} CI) 3.24-5.99], and P = 3.76 × 10-9, OR 2.47 [95{\%} CI 1.82-3.36], respectively). The RPEs test showed that the DRB1*0401 and *0410 alleles conferred susceptibility and that the DRB1*0701, *0802, *1301, *1302, *1403, and *1405 alleles showed significant protective effects. Susceptibility and protective alleles both showed a pattern consistent with additive genetic effects, and each influenced RA independently of the other. The compound heterozygote DRB1*0405/ *0901 was associated with the highest risk of RA (corrected P = 1.81 × 10-11, OR 58.2 [95{\%} CI 7.95-425.70]). The mean age at disease onset was ∼4 years earlier or was 3 years earlier, respectively, in patients with at least 1 copy of the DRB1*0405 or the DRB1*0901 allele. Radiographic changes (stages II-IV) were more frequent in patients with at least 1 copy of DRB1*0405 (P = 0.032, 92.6{\%} versus §4.3{\%}, OR 2.33 [95{\%} CI 1.24-4.39]). Conclusion. The DRB1*0405/*0901 heterozygote has the strongest association with RA, suggesting that this heterozygote enhances the susceptibility to RA in Koreans.",
author = "Lee, {Hye Soon} and Lee, {Kyung Wha} and Song, {Gwan Gyu} and Kim, {Hyun Ah} and Kim, {Shin Yoon} and Bae, {Sang Cheol}",
year = "2004",
month = "11",
day = "1",
doi = "10.1002/art.20608",
language = "English",
volume = "50",
pages = "3468--3475",
journal = "Arthritis and Rheumatology",
issn = "2326-5191",
publisher = "John Wiley and Sons Ltd",
number = "11",

}

TY - JOUR

T1 - Increased susceptibility to rheumatoid arthritis in koreans heterozygous for HLA-DRB1*0405 and *0901

AU - Lee, Hye Soon

AU - Lee, Kyung Wha

AU - Song, Gwan Gyu

AU - Kim, Hyun Ah

AU - Kim, Shin Yoon

AU - Bae, Sang Cheol

PY - 2004/11/1

Y1 - 2004/11/1

N2 - Objective. To investigate the association of susceptibility and protective HLA-DRB1 alleles with rheumatoid arthritis (RA) and its clinical markers in an Asian population. Methods. All RA patients (n = 574) and control subjects (n = 392) were Korean. HLA-DRB1 typing and further subtyping of all alleles was performed by polymerase chain reaction, sequence-specific oligonucleotide probe hybridization, and direct DNA sequencing analysis. We used a relative predispositional effects (RPEs) method and a false discovery rate correction method for multiple comparisons. Results. The DRB1*0405 and *0901 alleles showed the most significant associations with RA (P = 7.83 × 1024, odds ratio [OR] 4.40 [95% confidence interval (95% CI) 3.24-5.99], and P = 3.76 × 10-9, OR 2.47 [95% CI 1.82-3.36], respectively). The RPEs test showed that the DRB1*0401 and *0410 alleles conferred susceptibility and that the DRB1*0701, *0802, *1301, *1302, *1403, and *1405 alleles showed significant protective effects. Susceptibility and protective alleles both showed a pattern consistent with additive genetic effects, and each influenced RA independently of the other. The compound heterozygote DRB1*0405/ *0901 was associated with the highest risk of RA (corrected P = 1.81 × 10-11, OR 58.2 [95% CI 7.95-425.70]). The mean age at disease onset was ∼4 years earlier or was 3 years earlier, respectively, in patients with at least 1 copy of the DRB1*0405 or the DRB1*0901 allele. Radiographic changes (stages II-IV) were more frequent in patients with at least 1 copy of DRB1*0405 (P = 0.032, 92.6% versus §4.3%, OR 2.33 [95% CI 1.24-4.39]). Conclusion. The DRB1*0405/*0901 heterozygote has the strongest association with RA, suggesting that this heterozygote enhances the susceptibility to RA in Koreans.

AB - Objective. To investigate the association of susceptibility and protective HLA-DRB1 alleles with rheumatoid arthritis (RA) and its clinical markers in an Asian population. Methods. All RA patients (n = 574) and control subjects (n = 392) were Korean. HLA-DRB1 typing and further subtyping of all alleles was performed by polymerase chain reaction, sequence-specific oligonucleotide probe hybridization, and direct DNA sequencing analysis. We used a relative predispositional effects (RPEs) method and a false discovery rate correction method for multiple comparisons. Results. The DRB1*0405 and *0901 alleles showed the most significant associations with RA (P = 7.83 × 1024, odds ratio [OR] 4.40 [95% confidence interval (95% CI) 3.24-5.99], and P = 3.76 × 10-9, OR 2.47 [95% CI 1.82-3.36], respectively). The RPEs test showed that the DRB1*0401 and *0410 alleles conferred susceptibility and that the DRB1*0701, *0802, *1301, *1302, *1403, and *1405 alleles showed significant protective effects. Susceptibility and protective alleles both showed a pattern consistent with additive genetic effects, and each influenced RA independently of the other. The compound heterozygote DRB1*0405/ *0901 was associated with the highest risk of RA (corrected P = 1.81 × 10-11, OR 58.2 [95% CI 7.95-425.70]). The mean age at disease onset was ∼4 years earlier or was 3 years earlier, respectively, in patients with at least 1 copy of the DRB1*0405 or the DRB1*0901 allele. Radiographic changes (stages II-IV) were more frequent in patients with at least 1 copy of DRB1*0405 (P = 0.032, 92.6% versus §4.3%, OR 2.33 [95% CI 1.24-4.39]). Conclusion. The DRB1*0405/*0901 heterozygote has the strongest association with RA, suggesting that this heterozygote enhances the susceptibility to RA in Koreans.

UR - http://www.scopus.com/inward/record.url?scp=8444224296&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=8444224296&partnerID=8YFLogxK

U2 - 10.1002/art.20608

DO - 10.1002/art.20608

M3 - Article

C2 - 15529363

AN - SCOPUS:8444224296

VL - 50

SP - 3468

EP - 3475

JO - Arthritis and Rheumatology

JF - Arthritis and Rheumatology

SN - 2326-5191

IS - 11

ER -