{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T22:35:10Z","timestamp":1790289310963,"version":"4.1.0"},"reference-count":17,"publisher":"The Journal of Rheumatology","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Rheumatol"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:sec><jats:title>Objective.<\/jats:title><jats:p>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).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods.<\/jats:title><jats:p>High-resolution<jats:italic>HLA-DRB1<\/jats:italic>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results.<\/jats:title><jats:p>Of the 29 amino acid positions examined, positions 11, 13, and 33 (permutation p = 3.4<jats:sup>e-26<\/jats:sup>, 1.2<jats:sup>e-27<\/jats:sup>, and 2.1<jats:sup>e-28<\/jats:sup>, 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\u20137.0) and histidine at position 13 (OR 6.1, 95% CI 4.2\u20138.6) 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\u20137.61) and conversely the haplotype with serine at this position, S_K_R, conferred the most protection (OR 0.83, 95% CI 0.61\u20131.15).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion.<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.3899\/jrheum.180107","type":"journal-article","created":{"date-parts":[[2018,11,1]],"date-time":"2018-11-01T07:15:26Z","timestamp":1541056526000},"page":"138-144","source":"Crossref","is-referenced-by-count":9,"title":["HLA-DRB1 Amino Acid Positions and Residues Associated with Antibody-positive Rheumatoid Arthritis in Black South Africans"],"prefix":"10.3899","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2900-1042","authenticated-orcid":false,"given":"Nimmisha","family":"Govind","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6419-7779","authenticated-orcid":false,"given":"Richard J.","family":"Reynolds","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5360-9483","authenticated-orcid":false,"given":"Bridget","family":"Hodkinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1295-6424","authenticated-orcid":false,"given":"Claudia","family":"Ickinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4156-4801","authenticated-orcid":false,"given":"Michele","family":"Ramsay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3785-1389","authenticated-orcid":false,"suffix":"Jr.","given":"S. Louis","family":"Bridges","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7850-3538","authenticated-orcid":false,"given":"Mohammed","family":"Tikly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2262","published-online":{"date-parts":[[2018,11,1]]},"reference":[{"key":"2019020109251869000_46.2.138.1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/30.2.151"},{"key":"2019020109251869000_46.2.138.2","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1111\/j.1399-0004.1989.tb03185.x","article-title":"The contribution of HLA to rheumatoid arthritis","volume":"36","author":"Deighton","year":"1989","journal-title":"Clin Genet"},{"key":"2019020109251869000_46.2.138.3","first-page":"1326","article-title":"HLA associations with rheumatoid arthritis in African blacks","volume":"16","author":"Mody","year":"1989","journal-title":"J Rheumatol"},{"key":"2019020109251869000_46.2.138.4","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1111\/j.1399-0039.1992.tb01924.x","article-title":"HLA-DR antigens and rheumatoid arthritis in black South Africans: A study of ethnic groups","volume":"39","author":"Pile","year":"1992","journal-title":"Tissue Antigens"},{"key":"2019020109251869000_46.2.138.5","doi-asserted-by":"publisher","DOI":"10.1186\/ar3479"},{"key":"2019020109251869000_46.2.138.6","doi-asserted-by":"crossref","first-page":"341","DOI":"10.2119\/molmed.2014.00097","article-title":"Immunochip identifies novel, and replicates known, genetic risk loci for rheumatoid arthritis in black South Africans","volume":"20","author":"Govind","year":"2014","journal-title":"Mol Med"},{"key":"2019020109251869000_46.2.138.7","doi-asserted-by":"publisher","DOI":"10.1002\/art.23166"},{"key":"2019020109251869000_46.2.138.8","doi-asserted-by":"publisher","DOI":"10.1186\/ar2945"},{"key":"2019020109251869000_46.2.138.9","doi-asserted-by":"publisher","DOI":"10.1038\/ng.1076"},{"key":"2019020109251869000_46.2.138.10","doi-asserted-by":"crossref","first-page":"3274","DOI":"10.1002\/art.38855","article-title":"HLA-DRB1-associated rheumatoid arthritis risk at multiple levels in African Americans: hierarchical classification systems, amino acid positions, and residues","volume":"66","author":"Reynolds","year":"2014","journal-title":"Arthritis Rheumatol"},{"key":"2019020109251869000_46.2.138.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2007.01.014"},{"key":"2019020109251869000_46.2.138.12","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0064683"},{"key":"2019020109251869000_46.2.138.13","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-14-644"},{"key":"2019020109251869000_46.2.138.14","doi-asserted-by":"publisher","DOI":"10.1038\/gene.2011.79"},{"key":"2019020109251869000_46.2.138.15","doi-asserted-by":"crossref","first-page":"2618","DOI":"10.1002\/art.39780","article-title":"HLA-DRB1 amino acid positions 11\/13, 71, and 74 are associated with inflammation level, disease activity, and the health assessment questionnaire score in patients with inflammatory polyarthritis","volume":"68","author":"Ling","year":"2016","journal-title":"Arthritis Rheumatol"},{"key":"2019020109251869000_46.2.138.16","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1002\/art.39018","article-title":"Association of valine and leucine at HLA-DRB1 position 11 with radiographic progression in rheumatoid arthritis, independent of the shared epitope alleles but not independent of anti-citrullinated protein antibodies","volume":"67","author":"van Steenbergen","year":"2015","journal-title":"Arthritis Rheumatol"},{"key":"2019020109251869000_46.2.138.17","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.3435"}],"container-title":["The Journal of Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.3899\/jrheum.180107","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,10,30]],"date-time":"2019-10-30T07:57:38Z","timestamp":1572422258000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.jrheum.org\/lookup\/doi\/10.3899\/jrheum.180107"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,1]]},"references-count":17,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2019,2,1]]},"published-print":{"date-parts":[[2019,2]]}},"alternative-id":["10.3899\/jrheum.180107"],"URL":"https:\/\/doi.org\/10.3899\/jrheum.180107","relation":{},"ISSN":["0315-162X","1499-2752"],"issn-type":[{"value":"0315-162X","type":"print"},{"value":"1499-2752","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,1]]}}}