{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T01:25:48Z","timestamp":1789349148580,"version":"build-2803163510"},"reference-count":49,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2007,4,27]],"date-time":"2007-04-27T00:00:00Z","timestamp":1177632000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2007,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To determine whether the HLA\u2013DRB1 shared epitope (SE) is associated with early mortality and specific causes of death in rheumatoid arthritis (RA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>HLA\u2013DRB1 genotyping was carried out on blood samples from 767 patients recruited for the Early RA Study (ERAS), a multicenter, inception cohort study with followup over 18 years. Dates and causes of death (n = 186) were obtained from the Office of National Statistics. The association of HLA\u2013DRB1 alleles with risk of mortality was assessed using Cox proportional hazards regression analyses. Multivariate stepwise models were used to assess the predictive value of HLA\u2013DRB1 genotypes compared with other potential baseline risk factors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The SE was not significantly associated with overall mortality. However, the presence of 2 SE alleles was associated with risk of mortality from ischemic heart disease (hazard ratio [HR] 2.02 [95% confidence interval 1.04\u20133.94], <jats:italic>P<\/jats:italic> = 0.04), and malignancy (HR 2.18 [95% confidence interval 1.17\u20134.08], <jats:italic>P<\/jats:italic> = 0.01). Analysis of specific SE genotypes (corrected for age and sex) revealed that the HLA\u2013DRB1*0101\/*0401 and 0404\/*0404 genotypes were the strongest predictors of mortality from ischemic heart disease (HR 5.11 and HR 7.55, respectively), and DRB1*0101\/*0401 showed a possible interaction with smoking. Male sex, erythrocyte sedimentation rate, and Carstairs Deprivation Index were also predictive, but the Health Assessment Questionnaire score, rheumatoid factor, nodules, and swollen joint counts were not. Mortality due to malignancy was particularly associated with DRB1*0101 genotypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The risk of mortality due to ischemic heart disease or cancer in RA is increased in patients carrying HLA\u2013DRB1 genotypes with particular homozygous and compound heterozygous SE combinations.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.22527","type":"journal-article","created":{"date-parts":[[2007,4,27]],"date-time":"2007-04-27T17:18:39Z","timestamp":1177694319000},"page":"1408-1416","source":"Crossref","is-referenced-by-count":68,"title":["Association of DRB1 shared epitope genotypes with early mortality in rheumatoid arthritis: Results of eighteen years of followup from the early rheumatoid arthritis study"],"prefix":"10.1002","volume":"56","author":[{"given":"D. L.","family":"Mattey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.","family":"Thomson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. E. R.","family":"Ollier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Batley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. G.","family":"Davies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. K.","family":"Gough","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Devlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Prouse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. W.","family":"James","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. L.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Dixey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Winfield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N. L.","family":"Cox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Koduri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Young","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,4,27]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/23.2.92"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/27.1.44"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.49.6.363"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780370408"},{"key":"e_1_2_7_6_2","first-page":"445","article-title":"Cardiovascular morbidity and mortality in patients with seropositive rheumatoid arthritis in Northern Sweden","volume":"24","author":"Wallberg\u2010Jonsson S","year":"1997","journal-title":"J Rheumatol"},{"key":"e_1_2_7_7_2","first-page":"2562","article-title":"Extent of inflammation predicts cardiovascular disease and overall mortality in seropositive rheumatoid arthritis: a retrospective cohort study from disease onset","volume":"26","author":"Wallberg\u2010Jonsson S","year":"1999","journal-title":"J Rheumatol"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/40.4.447"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.61.11.994"},{"key":"e_1_2_7_10_2","first-page":"62","article-title":"Occurrence of extraarticular disease manifestations is associated with excess mortality in a community based cohort of patients with rheumatoid arthritis","volume":"29","author":"Turesson C","year":"2002","journal-title":"J Rheumatol"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2004.034777"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.20878"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kel253"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000099844.31524.05"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.20636"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21288"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21397"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780301102"},{"key":"e_1_2_7_19_2","first-page":"1032","article-title":"HLA\u2010DRB1*0401\/0404 genotype and rheumatoid arthritis: increased association in men, young age at onset and disease severity","volume":"22","author":"MacGregor A","year":"1995","journal-title":"J Rheumatol"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115814"},{"key":"e_1_2_7_21_2","first-page":"1272","article-title":"Role of HLA\u2010DR\u2010DR and DR\u2010DQ associations in the expression of extraarticular manifestations and rheumatoid factor in rheumatoid arthritis","volume":"24","author":"Perdriger A","year":"1997","journal-title":"J Rheumatol"},{"key":"e_1_2_7_22_2","first-page":"2313","article-title":"Nodular disease in rheumatoid arthritis: association with cigarette smoking and HLA\u2010DRB1\/TNF gene interaction","volume":"29","author":"Mattey DL","year":"2002","journal-title":"J Rheumatol"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.20588"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(03)00133-5"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/39.6.603"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.59.10.794"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780310302"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1949.02900430001001"},{"key":"e_1_2_7_29_2","first-page":"789","article-title":"Dimensions of health outcomes: the Health Assessment Questionnaire, disability and pain scales","volume":"9","author":"Fries J","year":"1982","journal-title":"J Rheumatol"},{"issue":"69","key":"e_1_2_7_30_2","first-page":"48","article-title":"Is it possible to predict radiological damage in early rheumatoid arthritis (RA)? A report on the occurrence, progression, and prognostic factors of radiological erosions over the first 3 years in 866 patients from the Early RA Study (ERAS)","volume":"31","author":"Dixey J","year":"2004","journal-title":"J Rheumatol"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1136\/jech.49.Suppl_2.S3"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keh059"},{"key":"e_1_2_7_33_2","volume-title":"International classification of diseases. 9th revision","year":"1977"},{"key":"e_1_2_7_34_2","first-page":"76","article-title":"Guidelines and audit measures for the specialist supervision of patients with rheumatoid arthritis","volume":"26","author":"Joint Working Group of the British Society of Rheumatology and Royal College of Physicians","year":"1992","journal-title":"J R Coll Physicians Lond"},{"key":"e_1_2_7_35_2","first-page":"70","article-title":"A comparative study of HLA\u2010DR4 subtyping by SSCP versus sequencing\u2010based typing and INNO\u2010LiPA strips","volume":"24","author":"Dababneh F","year":"1997","journal-title":"Eur J Immunogenet"},{"key":"e_1_2_7_36_2","doi-asserted-by":"publisher","DOI":"10.1177\/028418517701800415"},{"key":"e_1_2_7_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.20853"},{"key":"e_1_2_7_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(97)00101-9"},{"key":"e_1_2_7_39_2","first-page":"221","article-title":"Genetic predictors of coronary heart disease risk factors in premenopausal African\u2010American women","volume":"15","author":"Giger JN","year":"2005","journal-title":"Ethn Dis"},{"key":"e_1_2_7_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2005.10.001"},{"key":"e_1_2_7_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1047"},{"key":"e_1_2_7_42_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004320050207"},{"key":"e_1_2_7_43_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-02-0654"},{"key":"e_1_2_7_44_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00251-004-0723-9"},{"key":"e_1_2_7_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/0959-8049(96)00210-9"},{"key":"e_1_2_7_46_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0215(20001101)88:3<497::AID-IJC27>3.0.CO;2-J"},{"key":"e_1_2_7_47_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.20553"},{"key":"e_1_2_7_48_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2005.049676"},{"key":"e_1_2_7_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)08213-2"},{"key":"e_1_2_7_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2003.09.039"}],"container-title":["Arthritis &amp; Rheumatism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.22527","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.22527","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T21:56:08Z","timestamp":1698789368000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/art.22527"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,4,27]]},"references-count":49,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2007,5]]}},"alternative-id":["10.1002\/art.22527"],"URL":"https:\/\/doi.org\/10.1002\/art.22527","archive":["Portico"],"relation":{},"ISSN":["0004-3591","1529-0131"],"issn-type":[{"value":"0004-3591","type":"print"},{"value":"1529-0131","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,4,27]]}}}