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. 1995 Dec;54(12):988–990. doi: 10.1136/ard.54.12.988

Predominance of HLA-DRB1*0405 in Korean patients with rheumatoid arthritis.

H Y Kim 1, T G Kim 1, S H Park 1, S H Lee 1, C S Cho 1, H Han 1
PMCID: PMC1010065  PMID: 8546532

Abstract

OBJECTIVE--To identify the association of HLA-DR4 subtypes with rheumatoid arthritis (RA) in Koreans. METHODS--Ninety five patients with RA and 118 normal control subjects were examined for HLA-DR antigens by serology. Subtypes of HLA-DR4 were determined by allele specific oligonucleotide typing. RESULTS--The phenotype frequency of HLA-DR4 in RA patients was significantly greater than that in controls (60.0% versus 31.4%, odds ratio (OR) 3.28, 95% confidence interval (CI) 1.79 to 6.02 (p < 0.001)), but HLA-DR6 was decreased in RA patients (15.8% versus 32.2%, OR 0.39, 95% CI 0.19 to 0.81 (p < 0.001)). When DR4 was excluded from analysis of patients and controls, the allele frequency of DR1 was significantly increased in the patients compared with controls (11.3% versus 4.5%, OR 2.73, 95% CI 0.87 to 5.95 (p < 0.001)). Forty two of 57 DR4 positive patients (73.7%) possessed DRB1*0405, which was strongly associated with RA (44.2% of patients, versus 11.9% of controls: OR 5.88, 95% CI 2.81 to 12.47 (p < 0.001)). DRB1*0403 was not found in the patients, but was present in 8.5% of controls. Examining the third hyper-variable region at position 70-74 in the DRB1*04 chain by oligotyping, we found that 52 of 57 DR4 positive patients (91.2%) carried one of the conserved amino acid sequences QRRAA or QKRAA, known to be the epitope conferring predisposition to RA. CONCLUSION--This study confirms that RA is strongly associated with DR4, especially with DRB1*0405, and that the presence of the inferred QRRAA sequence may be important in susceptibility to RA in Koreans.

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Selected References

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  1. Chan S. H., Lin Y. N., Wee G. B., Koh W. H., Boey M. L. HLA class 2 genes in Singaporean Chinese rheumatoid arthritis. Br J Rheumatol. 1994 Aug;33(8):713–717. doi: 10.1093/rheumatology/33.8.713. [DOI] [PubMed] [Google Scholar]
  2. Gao X. J., Olsen N. J., Pincus T., Stastny P. HLA-DR alleles with naturally occurring amino acid substitutions and risk for development of rheumatoid arthritis. Arthritis Rheum. 1990 Jul;33(7):939–946. doi: 10.1002/art.1780330704. [DOI] [PubMed] [Google Scholar]
  3. Gregersen P. K., Silver J., Winchester R. J. The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum. 1987 Nov;30(11):1205–1213. doi: 10.1002/art.1780301102. [DOI] [PubMed] [Google Scholar]
  4. HALDANE J. B. The estimation and significance of the logarithm of a ratio of frequencies. Ann Hum Genet. 1956 May;20(4):309–311. doi: 10.1111/j.1469-1809.1955.tb01285.x. [DOI] [PubMed] [Google Scholar]
  5. Molkentin J., Gregersen P. K., Lin X., Zhu N., Wang Y., Wang Y., Chen S., Chen S., Baxter-Lowe L. A., Silver J. Molecular analysis of HLA-DR beta and DQ beta polymorphism in Chinese with rheumatoid arthritis. Ann Rheum Dis. 1993 Aug;52(8):610–612. doi: 10.1136/ard.52.8.610. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Okubo H., Itou K., Tanaka S., Watanabe N., Kashiwagi N., Obata F. Analysis of the HLA-DR gene frequencies in Japanese cases of juveniles rheumatoid arthritis and rheumatoid arthritis by oligonucleotide DNA typing. Rheumatol Int. 1993;13(2):65–69. doi: 10.1007/BF00307736. [DOI] [PubMed] [Google Scholar]
  7. Payami H., Joe S., Farid N. R., Stenszky V., Chan S. H., Yeo P. P., Cheah J. S., Thomson G. Relative predispositional effects (RPEs) of marker alleles with disease: HLA-DR alleles and Graves disease. Am J Hum Genet. 1989 Oct;45(4):541–546. [PMC free article] [PubMed] [Google Scholar]
  8. Seglias J., Li E. K., Cohen M. G., Wong R. W., Potter P. K., So A. K. Linkage between rheumatoid arthritis susceptibility and the presence of HLA-DR4 and DR beta allelic third hypervariable region sequences in southern Chinese persons. Arthritis Rheum. 1992 Feb;35(2):163–167. doi: 10.1002/art.1780350207. [DOI] [PubMed] [Google Scholar]
  9. Watanabe Y., Tokunaga K., Matsuki K., Takeuchi F., Matsuta K., Maeda H., Omoto K., Juji T. Putative amino acid sequence of HLA-DRB chain contributing to rheumatoid arthritis susceptibility. J Exp Med. 1989 Jun 1;169(6):2263–2268. doi: 10.1084/jem.169.6.2263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Wordsworth B. P., Bell J. I. The immunogenetics of rheumatoid arthritis. Springer Semin Immunopathol. 1992;14(1):59–78. doi: 10.1007/BF00197132. [DOI] [PubMed] [Google Scholar]
  11. Wordsworth B. P., Stedeford J., Rosenberg W. M., Bell J. I. Limited heterogeneity of the HLA class II contribution to susceptibility to rheumatoid arthritis is suggested by positive associations with HLA-DR4, DR1 and DRw10. Br J Rheumatol. 1991 Jun;30(3):178–180. doi: 10.1093/rheumatology/30.3.178. [DOI] [PubMed] [Google Scholar]

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