期刊
JOURNAL OF RHEUMATOLOGY
卷 46, 期 2, 页码 138-144出版社
J RHEUMATOL PUBL CO
DOI: 10.3899/jrheum.180107
关键词
VALINE; SERINE; HAPLOTYPES; ANTICITRULLINATED PEPTIDE ANTIBODY
类别
资金
- Carnegie Corporation of New York [B8749]
- Connective Tissue Diseases Fund
- University of the Witwatersrand
- Medical Research Council of South Africa
- National Research Foundation of South Africa
- US National Institutes of Health [K01 AR060848]
Objective. To investigate the association of specific amino acid positions, residues, and haplotypes of HLA-DRB1 in black South Africans with autoantibody-positive rheumatoid arthritis (RA). Methods. High-resolution HLA-DRB1 genotyping was performed in 266 black South Africans with autoantibody-positive RA and 362 ethnically and geographically matched controls. The alleles were converted to specific amino acid residues at polymorphic sites for downstream analyses. Logistic regression models were used to test whether variability at site, specific amino acid residues, and haplotypes (constructed from positions 11, 71, and 74) were associated with RA. Results. Of the 29 amino acid positions examined, positions 11, 13, and 33 (permutation p = 3.4(e-26), 1.2(e-27), and 2.1(e-28), respectively) showed the strongest association with RA. Univariate analyses of individual amino acid residues showed valine at position 11 (OR 5.1, 95% CI 3.7-7.0) and histidine at position 13 (OR 6.1, 95% CI 4.2-8.6) conferred the highest risk. The valine containing haplotypes of position 11, 71, 74, V_K_A conferred the most risk (OR 4.52, 95% CI 2.68-7.61) and conversely the haplotype with serine at this position, S_K_R, conferred the most protection (OR 0.83, 95% CI 0.61-1.15). Conclusion. Autoantibody-positive RA in black South Africans is associated with histidine at position 13 and valine at position 11 of HLA-DRB1, and haplotypes with valine at position 11 conferred the highest risk; conversely, serine at position 11 conveyed protection.
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