{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T05:32:20Z","timestamp":1791091940942,"version":"4.1.0"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2006,1,16]],"date-time":"2006-01-16T00:00:00Z","timestamp":1137369600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"},{"start":{"date-parts":[[2006,1,16]],"date-time":"2006-01-16T00:00:00Z","timestamp":1137369600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arthritis Res Ther"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Peptidylarginine deiminase type 4 (<jats:italic>PADI4<\/jats:italic>) genotypes were shown to influence susceptibility to rheumatoid arthritis (RA) in the Japanese population. Such an association could not previously be confirmed in different European populations. In the present study, we analysed exons 2\u20134 of <jats:italic>PADI4<\/jats:italic> in 102 German RA patients and 102 healthy individuals to study the influence of <jats:italic>PADI4<\/jats:italic> variability on RA susceptibility by means of haplotype-specific DNA sequencing. Analyses of the influence of <jats:italic>PADI4<\/jats:italic> and <jats:italic>HLA-DRB1<\/jats:italic> genotypes on disease activity and on levels of anti-cyclic citrullinated peptide antibodies were performed.<\/jats:p><jats:p>Comparing the frequencies of <jats:italic>PADI4<\/jats:italic> haplotype 4 (padi4_89*G, padi4_90*T, padi4_92*G, padi4_94*T, padi4_104*C, padi4_95*G, padi4_96*T) (patients, 14.7%; controls, 7.8%; odds ratio = 2.0, 95% confidence interval = 1.1\u20133.8) and carriers of this haplotype (patients, 27.5%; controls, 13.7%; odds ratio = 2.4, 95% confidence interval = 1.2\u20134.8), a significant positive association of <jats:italic>PADI4<\/jats:italic> haplotype 4 with RA could be demonstrated. Other <jats:italic>PADI4<\/jats:italic> haplotypes did not differ significantly between patients and controls. Regarding the individual <jats:italic>PADI4<\/jats:italic> variants, padi4_89 (A\u2192G), padi4_90 (C\u2192T), and padi4_94 (C\u2192T) were significantly associated with RA (patients, 49.5%; controls, 38.7%; odds ratio = 1.6, 95% confidence interval = 1.1\u20132.3). Considering novel <jats:italic>PADI4<\/jats:italic> variants located in or near to exons 2, 3, and 4, no quantitative or qualitative differences between RA patients (8.8%) and healthy controls (10.8%) could be demonstrated. While the <jats:italic>PADI4<\/jats:italic> genotype did not influence disease activity and the anti-cyclic citrullinated peptide antibody level, the presence of the HLA-DRB1 shared epitope was significantly associated with higher anti-cyclic citrullinated peptide antibody levels (<jats:italic>P<\/jats:italic> = 0.033).<\/jats:p><jats:p>The results of this small case\u2013control study support the hypothesis that variability of the <jats:italic>PADI4<\/jats:italic> gene may influence susceptibility to RA in the German population. Quantitative or qualitative differences in previously undefined <jats:italic>PADI4<\/jats:italic> variants between patients and controls could not be demonstrated.<\/jats:p>","DOI":"10.1186\/ar1889","type":"journal-article","created":{"date-parts":[[2006,1,23]],"date-time":"2006-01-23T13:04:26Z","timestamp":1138021466000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Detailed analysis of the variability of peptidylarginine deiminase type 4 in German patients with rheumatoid arthritis: a case\u2013control study"],"prefix":"10.1186","volume":"8","author":[{"given":"Berthold","family":"Hoppe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"H\u00e4upl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf","family":"Gruber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Kiesewetter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerd R","family":"Burmester","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulgabar","family":"Salama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"D\u00f6rner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2006,1,16]]},"reference":[{"key":"1767_CR1","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.gene.2003.12.038","volume":"330","author":"S Chavanas","year":"2004","unstructured":"Chavanas S, Mechin MC, Takahara H, Kawada A, Nachat R, Serre G, Simon M: Comparative analysis of the mouse and human peptidylarginine deiminase gene clusters reveals highly conserved non-coding segments and a new human gene, PADI6. Gene. 2004, 330: 19-27. 10.1016\/j.gene.2003.12.038.","journal-title":"Gene"},{"key":"1767_CR2","doi-asserted-by":"crossref","first-page":"585","DOI":"10.4049\/jimmunol.162.1.585","volume":"162","author":"E Girbal-Neuhauser","year":"1999","unstructured":"Girbal-Neuhauser E, Durieux JJ, Arnaud M, Dalbon P, Sebbag M, Vincent C, Simon M, Senshu T, Masson-Bessiere C, Jolivet-Reynaud C, et al: The epitopes targeted by the rheumatoid arthritis-associated antifilaggrin autoantibodies are posttranslationally generated on various sites of (pro)filaggrin by deimination of arginine residues. 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