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 x 10(-24), odds ratio [OR] 4.40 [95% confidence interval (95% CI) 3.24-5.99], and P = 3.76 x 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 x 10(-11), OR 58.2 [95% CI 7.95-425.70]). The mean age at disease onset was approximately 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.

• Authors: Hye-Soon Lee, Kyung Wha Lee, Gwan Gyu Song, Hyun-Ah Kim, Shin-Yoon Kim, Sang-Cheol Bae
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 50 Issue 11 Pg. 3468-75 (Nov 2004) ISSN: 0004-3591 [Print] United States
• PMID: 15529363 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• HLA-DR Antigens
• HLA-DRB1 Chains
• HLA-DRB1*04:05 antigen
• HLA-DRB1*09:01 antigen

Topics

• Adult
• Alleles
• Arthritis, Rheumatoid (genetics)
• Asian People (genetics)
• Female
• Gene Frequency
• Genetic Predisposition to Disease
• Genotype
• HLA-DR Antigens (genetics)
• HLA-DRB1 Chains
• Heterozygote
• Humans
• Male
• Middle Aged