Research Article
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,
Hye-Soon Lee
Hanyang University College of Medicine, Hospital for Rheumatic Diseases, Seoul, South Korea
Drs. Hye-Soon Lee and Kyung Wha Lee contributed equally to this work.
Search for more papers by this authorKyung Wha Lee
Hallym Institution for Genome Application, Hallym University Sacred Heart Hospital, Anyang, South Korea
Drs. Hye-Soon Lee and Kyung Wha Lee contributed equally to this work.
Search for more papers by this authorGwan Gyu Song
College of Medicine, Korea University, Seoul, South Korea
Search for more papers by this authorHyun-Ah Kim
Hallym University Kangdong Sacred Heart Hospital, Seoul, South Korea
Search for more papers by this authorShin-Yoon Kim
Kyungpook National University College of Medicine, Daegu, South Korea
Search for more papers by this authorCorresponding Author
Sang-Cheol Bae
Hanyang University College of Medicine, Hospital for Rheumatic Diseases, Seoul, South Korea
Hospital for Rheumatic Diseases, Hanyang University Medical Center, Seoul 133-792, South KoreaSearch for more papers by this authorHye-Soon Lee,
Kyung Wha Lee,
Gwan Gyu Song,
Hyun-Ah Kim,
Shin-Yoon Kim,
Sang-Cheol Bae,
Hye-Soon Lee
Hanyang University College of Medicine, Hospital for Rheumatic Diseases, Seoul, South Korea
Drs. Hye-Soon Lee and Kyung Wha Lee contributed equally to this work.
Search for more papers by this authorKyung Wha Lee
Hallym Institution for Genome Application, Hallym University Sacred Heart Hospital, Anyang, South Korea
Drs. Hye-Soon Lee and Kyung Wha Lee contributed equally to this work.
Search for more papers by this authorGwan Gyu Song
College of Medicine, Korea University, Seoul, South Korea
Search for more papers by this authorHyun-Ah Kim
Hallym University Kangdong Sacred Heart Hospital, Seoul, South Korea
Search for more papers by this authorShin-Yoon Kim
Kyungpook National University College of Medicine, Daegu, South Korea
Search for more papers by this authorCorresponding Author
Sang-Cheol Bae
Hanyang University College of Medicine, Hospital for Rheumatic Diseases, Seoul, South Korea
Hospital for Rheumatic Diseases, Hanyang University Medical Center, Seoul 133-792, South KoreaSearch for more papers by this authorAbstract
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 × 10−24, 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 84.3%, 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.
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