{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T00:23:16Z","timestamp":1763684596637},"reference-count":32,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,2,25]],"date-time":"2013-02-25T00:00:00Z","timestamp":1361750400000},"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":[[2013,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Genetic factors account for an estimated 45\u201358% of the variance in joint destruction in rheumatoid arthritis (RA). The serine proteinase granzyme B induces target cell apoptosis, and several in vitro studies suggest that granzyme B is involved in apoptosis of chondrocytes. Serum levels of granzyme B are increased in RA and are also associated with radiographic erosions. The aim of this study was to investigate <jats:italic>GZMB<\/jats:italic> as a candidate gene accounting for the severity of joint destruction in RA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 1,418 patients with 4,885 radiograph sets of the hands and feet from 4 independent cohorts were studied. First, explorative analyses were performed in 600 RA patients in the Leiden Early Arthritis Clinic cohort. Fifteen single\u2010nucleotide polymorphisms (SNPs) tagging <jats:italic>GZMB<\/jats:italic> were tested. Significantly associated SNPs were genotyped in data sets representing patients from the Groningen, Sheffield, and Lund cohorts. In each data set, the relative increase in the annual rate of progression in the presence of a genotype was assessed. Data were summarized in a meta\u2010analysis. The association of <jats:italic>GZMB<\/jats:italic> with the RNA expression level of the <jats:italic>GZMB<\/jats:italic> genomic region was tested by mapping expression quantitative trait loci (QTLs) on 1,469 whole blood samples<jats:italic>.<\/jats:italic><\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>SNP rs8192916 was significantly associated with the rate of joint destruction in the first cohort and in the meta\u2010analysis of all data sets. Patients homozygous for the minor allele of rs8192916 had a higher rate of joint destruction per year compared with other patients (<jats:italic>P<\/jats:italic> = 7.8 \u00d7 10<jats:sup>\u22124<\/jats:sup>). Expression QTL of <jats:italic>GZMB<\/jats:italic> identified higher expression in the presence of the minor allele of rs8192916 (<jats:italic>P =<\/jats:italic> 2.27 \u00d7 10<jats:sup>\u22125<\/jats:sup>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>SNP rs8192916 located in <jats:italic>GZMB<\/jats:italic> is associated with the progression of joint destruction in RA as well as with RNA expression in whole blood.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.37808","type":"journal-article","created":{"date-parts":[[2012,12,13]],"date-time":"2012-12-13T18:58:04Z","timestamp":1355425084000},"page":"582-589","source":"Crossref","is-referenced-by-count":23,"title":["A genetic variant in granzyme B is associated with progression of joint destruction in rheumatoid arthritis"],"prefix":"10.1002","volume":"65","author":[{"given":"R.","family":"Knevel","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Krabben","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. G.","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Brouwer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. K.","family":"Leijsma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Lindqvist","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. P. C.","family":"de Rooy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N. A.","family":"Daha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. P. M.","family":"van der Linden","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Tsonaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Zhernakova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.\u2010J.","family":"Westra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Franke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. J.","family":"Houwing\u2010Duistermaat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. E. M.","family":"Toes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T. W. J.","family":"Huizinga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Saxne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. H. M.","family":"van der Helm\u2010van Mil","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,2,25]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/31.8.519"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keq230"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21872"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2011-200627"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(00)00094-7"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-065X.2003.00044.x"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.151.12.7161"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/40.1.55"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2011-200386"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.1999.00881.x"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2003.007039"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05911"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780310302"},{"key":"e_1_2_7_15_2","first-page":"175","article-title":"1958 revision of diagnostic criteria for rheumatoid arthritis","volume":"9","author":"Ropes MW","year":"1958","journal-title":"Bull Rheum Dis"},{"key":"e_1_2_7_16_2","first-page":"261","article-title":"How to read radiographs according to the Sharp\/van der Heijde method","volume":"27","author":"Van der Heijde D","year":"2000","journal-title":"J Rheumatol"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar2017"},{"key":"e_1_2_7_18_2","first-page":"1976","article-title":"A modified version of Larsen's scoring method to assess radiologic changes in rheumatoid arthritis","volume":"22","author":"Rau R","year":"1995","journal-title":"J Rheumatol"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/35.11.1106"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.62.7.611"},{"key":"e_1_2_7_21_2","first-page":"285","volume-title":"The recognition of anti\u2010rheumatic drugs","author":"Larsen A","year":"1978"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1669"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bth457"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.543"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002197"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000232"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1198\/jasa.2009.0116"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.61.suppl_2.ii64"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keq013"},{"key":"e_1_2_7_30_2","first-page":"269","article-title":"Pooled metaanalysis of radiographic progression: comparison of Sharp and Larsen methods","volume":"27","author":"Lassere M","year":"2000","journal-title":"J Rheumatol"},{"key":"e_1_2_7_31_2","doi-asserted-by":"crossref","first-page":"Article 8","DOI":"10.2202\/1544-6115.1503","article-title":"Dealing with heterogeneity between cohorts in genomewide SNP association studies","volume":"9","author":"Lebrec JJ","year":"2010","journal-title":"Stat Appl Genet Mol Biol"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(03)00107-9"},{"key":"e_1_2_7_33_2","first-page":"1932","article-title":"Granzyme B induces apoptosis of chondrocytes with natural killer cell\u2010like cytotoxicity in rheumatoid arthritis","volume":"35","author":"Saito S","year":"2008","journal-title":"J Rheumatol"}],"container-title":["Arthritis &amp; Rheumatism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.37808","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.37808","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T05:31:46Z","timestamp":1697607106000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/art.37808"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,2,25]]},"references-count":32,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2013,3]]}},"alternative-id":["10.1002\/art.37808"],"URL":"https:\/\/doi.org\/10.1002\/art.37808","archive":["Portico"],"relation":{},"ISSN":["0004-3591","1529-0131"],"issn-type":[{"value":"0004-3591","type":"print"},{"value":"1529-0131","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,2,25]]}}}