PADI2 is significantly associated with rheumatoid arthritis
Citrullination, a posttranslational modification of peptidyl arginine to citrulline, plays an essential role in rheumatoid arthritis (RA). Citrullination is catalyzed by a group of peptidylarginine deiminases (PADs) including PADI 1, 2, 3, 4 and 6. Many studies have indicated that the gene encoding...
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| description | Citrullination, a posttranslational modification of peptidyl arginine to citrulline, plays an essential role in rheumatoid arthritis (RA). Citrullination is catalyzed by a group of peptidylarginine deiminases (PADs) including PADI 1, 2, 3, 4 and 6. Many studies have indicated that the gene encoding PADI4 is a factor in susceptibility to RA. Some studies have detected PADI2 expression in RA synovial tissues, suggesting that PADI2 also plays an important role in the disease. This study evaluated the possible association between the PADI2-encoding gene and RA. Seventeen tag SNPs across the PAD locus were genotyped using a custom-designed Illumina 96-SNP VeraCode microarray. Peripheral blood samples were collected from patients with RA (n = 267), ankylosing spondylitis (AS, n = 51) and healthy controls (n = 160). The results of genotyping were verified using Sequenom MassARRAY in an independent cohort of 307 patients with RA, 324 patients with AS and 509 healthy controls. A western blot analysis was performed using synovial tissue from patients with RA (n = 7), osteoarthritis (OA, n = 7) and AS (n = 5) to determine the levels of expression of PADI2. A microarray analysis revealed a significant association between three selected PADI2 SNPs (rs2235926, rs2057094, rs2076616) and the presence of RA. The increased susceptibility to RA associated with rs2235926 (OR = 1.706733, 95% CI = [1.576366-1.866587], p = 0.000839) and rs2057094 (OR = 1.360432, 95% CI = [1.065483-1.869482], p = 0.003291) was further confirmed by the Sequenom MassARRAY. No tag SNPs in the PADI2 locus showed a significant association with AS. Increased expression of PADI2 was detected in RA synovial tissues compared with samples from patients with OA and AS. PADI2 is significantly associated with RA and may be involved in the pathogenesis of the disease. |
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Citrullination is catalyzed by a group of peptidylarginine deiminases (PADs) including PADI 1, 2, 3, 4 and 6. Many studies have indicated that the gene encoding PADI4 is a factor in susceptibility to RA. Some studies have detected PADI2 expression in RA synovial tissues, suggesting that PADI2 also plays an important role in the disease. This study evaluated the possible association between the PADI2-encoding gene and RA. Seventeen tag SNPs across the PAD locus were genotyped using a custom-designed Illumina 96-SNP VeraCode microarray. Peripheral blood samples were collected from patients with RA (n = 267), ankylosing spondylitis (AS, n = 51) and healthy controls (n = 160). The results of genotyping were verified using Sequenom MassARRAY in an independent cohort of 307 patients with RA, 324 patients with AS and 509 healthy controls. A western blot analysis was performed using synovial tissue from patients with RA (n = 7), osteoarthritis (OA, n = 7) and AS (n = 5) to determine the levels of expression of PADI2. A microarray analysis revealed a significant association between three selected PADI2 SNPs (rs2235926, rs2057094, rs2076616) and the presence of RA. The increased susceptibility to RA associated with rs2235926 (OR = 1.706733, 95% CI = [1.576366-1.866587], p = 0.000839) and rs2057094 (OR = 1.360432, 95% CI = [1.065483-1.869482], p = 0.003291) was further confirmed by the Sequenom MassARRAY. No tag SNPs in the PADI2 locus showed a significant association with AS. Increased expression of PADI2 was detected in RA synovial tissues compared with samples from patients with OA and AS. PADI2 is significantly associated with RA and may be involved in the pathogenesis of the disease.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0081259</identifier><identifier>PMID: 24339914</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Aged ; Analysis ; Ankylosing spondylitis ; Arginine ; Arthritis ; Arthritis, Rheumatoid - enzymology ; Arthritis, Rheumatoid - genetics ; Biocompatibility ; Biomedical materials ; Citrulline ; Consortia ; DNA microarrays ; Female ; Gene expression ; Gene Expression Regulation, Enzymologic ; Genes ; Genetic Loci - genetics ; Genetic Predisposition to Disease - genetics ; Genomes ; Genotyping ; Genotyping Techniques ; Haplotypes ; Humans ; Hydrolases - genetics ; Kinases ; Loci ; Male ; Medical research ; Middle Aged ; Osteoarthritis ; Pathogenesis ; Patients ; Peripheral blood ; Polymorphism, Single Nucleotide ; Protein-arginine deiminase ; Protein-Arginine Deiminases ; Proteins ; Rheumatoid arthritis ; Rheumatoid factor ; Risk factors ; Single nucleotide polymorphisms ; Single-nucleotide polymorphism ; Spondylitis ; Studies ; Synovial Membrane - metabolism ; Tissues</subject><ispartof>PloS one, 2013-12, Vol.8 (12), p.e81259-e81259</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Chang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/3.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Chang et al 2013 Chang et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-682b669da85a374dc1e38de8c99160d1f8da5623a629d79d194591ddd77bf55a3</citedby><cites>FETCH-LOGICAL-c692t-682b669da85a374dc1e38de8c99160d1f8da5623a629d79d194591ddd77bf55a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3855321/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3855321/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24339914$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chang, Xiaotian</creatorcontrib><creatorcontrib>Xia, Yifang</creatorcontrib><creatorcontrib>Pan, Jihong</creatorcontrib><creatorcontrib>Meng, Qingsong</creatorcontrib><creatorcontrib>Zhao, Yan</creatorcontrib><creatorcontrib>Yan, Xinfeng</creatorcontrib><title>PADI2 is significantly associated with rheumatoid arthritis</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Citrullination, a posttranslational modification of peptidyl arginine to citrulline, plays an essential role in rheumatoid arthritis (RA). Citrullination is catalyzed by a group of peptidylarginine deiminases (PADs) including PADI 1, 2, 3, 4 and 6. Many studies have indicated that the gene encoding PADI4 is a factor in susceptibility to RA. Some studies have detected PADI2 expression in RA synovial tissues, suggesting that PADI2 also plays an important role in the disease. This study evaluated the possible association between the PADI2-encoding gene and RA. Seventeen tag SNPs across the PAD locus were genotyped using a custom-designed Illumina 96-SNP VeraCode microarray. Peripheral blood samples were collected from patients with RA (n = 267), ankylosing spondylitis (AS, n = 51) and healthy controls (n = 160). The results of genotyping were verified using Sequenom MassARRAY in an independent cohort of 307 patients with RA, 324 patients with AS and 509 healthy controls. A western blot analysis was performed using synovial tissue from patients with RA (n = 7), osteoarthritis (OA, n = 7) and AS (n = 5) to determine the levels of expression of PADI2. A microarray analysis revealed a significant association between three selected PADI2 SNPs (rs2235926, rs2057094, rs2076616) and the presence of RA. The increased susceptibility to RA associated with rs2235926 (OR = 1.706733, 95% CI = [1.576366-1.866587], p = 0.000839) and rs2057094 (OR = 1.360432, 95% CI = [1.065483-1.869482], p = 0.003291) was further confirmed by the Sequenom MassARRAY. No tag SNPs in the PADI2 locus showed a significant association with AS. Increased expression of PADI2 was detected in RA synovial tissues compared with samples from patients with OA and AS. PADI2 is significantly associated with RA and may be involved in the pathogenesis of the disease.</description><subject>Adult</subject><subject>Aged</subject><subject>Analysis</subject><subject>Ankylosing spondylitis</subject><subject>Arginine</subject><subject>Arthritis</subject><subject>Arthritis, Rheumatoid - enzymology</subject><subject>Arthritis, Rheumatoid - genetics</subject><subject>Biocompatibility</subject><subject>Biomedical materials</subject><subject>Citrulline</subject><subject>Consortia</subject><subject>DNA microarrays</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Enzymologic</subject><subject>Genes</subject><subject>Genetic Loci - genetics</subject><subject>Genetic Predisposition to Disease - genetics</subject><subject>Genomes</subject><subject>Genotyping</subject><subject>Genotyping Techniques</subject><subject>Haplotypes</subject><subject>Humans</subject><subject>Hydrolases - genetics</subject><subject>Kinases</subject><subject>Loci</subject><subject>Male</subject><subject>Medical research</subject><subject>Middle Aged</subject><subject>Osteoarthritis</subject><subject>Pathogenesis</subject><subject>Patients</subject><subject>Peripheral blood</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Protein-arginine deiminase</subject><subject>Protein-Arginine Deiminases</subject><subject>Proteins</subject><subject>Rheumatoid arthritis</subject><subject>Rheumatoid factor</subject><subject>Risk factors</subject><subject>Single nucleotide polymorphisms</subject><subject>Single-nucleotide polymorphism</subject><subject>Spondylitis</subject><subject>Studies</subject><subject>Synovial Membrane - metabolism</subject><subject>Tissues</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNkltrFDEYhgdR7EH_geiAIHqxa86TIAhLPS0UKp5uQybJ7GSZnWyTTLX_3mx3WnakF5KLhOR533xf8hbFMwjmEFfw7doPoVfdfOt7OweAQ0TFg-IYCoxmDAH88GB9VJzEuAaAYs7Y4-IIEYyFgOS4ePd18WGJShfL6Fa9a5xWfequSxWj104la8rfLrVlaO2wUck7U6qQ2uCSi0-KR43qon06zqfFz08ff5x9mZ1ffF6eLc5nmgmUZoyjmjFhFKcKV8RoaDE3lutcAQMGNtwoyhBWDAlTCQMFoQIaY6qqbmjWnBYv9r7bzkc59h0lJIzmRgBBmVjuCePVWm6D26hwLb1y8mbDh5XMVTvdWWnrRqvGUgDqmqAKcQMgrg3FmDSqMTB7vR9vG-qNNdr2KahuYjo96V0rV_5KYk4pRjuD16NB8JeDjUluXNS261Rv_XBTt0CQc8oz-vIf9P7uRmqlcgOub3y-V-9M5YJUnECByM5rfg-Vh7Ebp3NIGpf3J4I3E0Fmkv2TVmqIUS6_f_t_9uLXlH11wLZWdamNvhuS832cgmQP6uBjDLa5e2QI5C7jt68hdxmXY8az7PnhB92JbkON_wKsp_Xb</recordid><startdate>20131205</startdate><enddate>20131205</enddate><creator>Chang, Xiaotian</creator><creator>Xia, Yifang</creator><creator>Pan, Jihong</creator><creator>Meng, Qingsong</creator><creator>Zhao, Yan</creator><creator>Yan, Xinfeng</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20131205</creationdate><title>PADI2 is significantly associated with rheumatoid arthritis</title><author>Chang, Xiaotian ; Xia, Yifang ; Pan, Jihong ; Meng, Qingsong ; Zhao, Yan ; Yan, Xinfeng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-682b669da85a374dc1e38de8c99160d1f8da5623a629d79d194591ddd77bf55a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Analysis</topic><topic>Ankylosing spondylitis</topic><topic>Arginine</topic><topic>Arthritis</topic><topic>Arthritis, Rheumatoid - enzymology</topic><topic>Arthritis, Rheumatoid - genetics</topic><topic>Biocompatibility</topic><topic>Biomedical materials</topic><topic>Citrulline</topic><topic>Consortia</topic><topic>DNA microarrays</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Enzymologic</topic><topic>Genes</topic><topic>Genetic Loci - genetics</topic><topic>Genetic Predisposition to Disease - genetics</topic><topic>Genomes</topic><topic>Genotyping</topic><topic>Genotyping Techniques</topic><topic>Haplotypes</topic><topic>Humans</topic><topic>Hydrolases - genetics</topic><topic>Kinases</topic><topic>Loci</topic><topic>Male</topic><topic>Medical research</topic><topic>Middle Aged</topic><topic>Osteoarthritis</topic><topic>Pathogenesis</topic><topic>Patients</topic><topic>Peripheral blood</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Protein-arginine deiminase</topic><topic>Protein-Arginine Deiminases</topic><topic>Proteins</topic><topic>Rheumatoid arthritis</topic><topic>Rheumatoid factor</topic><topic>Risk factors</topic><topic>Single nucleotide polymorphisms</topic><topic>Single-nucleotide polymorphism</topic><topic>Spondylitis</topic><topic>Studies</topic><topic>Synovial Membrane - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chang, Xiaotian</au><au>Xia, Yifang</au><au>Pan, Jihong</au><au>Meng, Qingsong</au><au>Zhao, Yan</au><au>Yan, Xinfeng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PADI2 is significantly associated with rheumatoid arthritis</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-12-05</date><risdate>2013</risdate><volume>8</volume><issue>12</issue><spage>e81259</spage><epage>e81259</epage><pages>e81259-e81259</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Citrullination, a posttranslational modification of peptidyl arginine to citrulline, plays an essential role in rheumatoid arthritis (RA). Citrullination is catalyzed by a group of peptidylarginine deiminases (PADs) including PADI 1, 2, 3, 4 and 6. Many studies have indicated that the gene encoding PADI4 is a factor in susceptibility to RA. Some studies have detected PADI2 expression in RA synovial tissues, suggesting that PADI2 also plays an important role in the disease. This study evaluated the possible association between the PADI2-encoding gene and RA. Seventeen tag SNPs across the PAD locus were genotyped using a custom-designed Illumina 96-SNP VeraCode microarray. Peripheral blood samples were collected from patients with RA (n = 267), ankylosing spondylitis (AS, n = 51) and healthy controls (n = 160). The results of genotyping were verified using Sequenom MassARRAY in an independent cohort of 307 patients with RA, 324 patients with AS and 509 healthy controls. A western blot analysis was performed using synovial tissue from patients with RA (n = 7), osteoarthritis (OA, n = 7) and AS (n = 5) to determine the levels of expression of PADI2. A microarray analysis revealed a significant association between three selected PADI2 SNPs (rs2235926, rs2057094, rs2076616) and the presence of RA. The increased susceptibility to RA associated with rs2235926 (OR = 1.706733, 95% CI = [1.576366-1.866587], p = 0.000839) and rs2057094 (OR = 1.360432, 95% CI = [1.065483-1.869482], p = 0.003291) was further confirmed by the Sequenom MassARRAY. No tag SNPs in the PADI2 locus showed a significant association with AS. Increased expression of PADI2 was detected in RA synovial tissues compared with samples from patients with OA and AS. PADI2 is significantly associated with RA and may be involved in the pathogenesis of the disease.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24339914</pmid><doi>10.1371/journal.pone.0081259</doi><tpages>e81259</tpages><oa>free_for_read</oa></addata></record> |
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| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adult Aged Analysis Ankylosing spondylitis Arginine Arthritis Arthritis, Rheumatoid - enzymology Arthritis, Rheumatoid - genetics Biocompatibility Biomedical materials Citrulline Consortia DNA microarrays Female Gene expression Gene Expression Regulation, Enzymologic Genes Genetic Loci - genetics Genetic Predisposition to Disease - genetics Genomes Genotyping Genotyping Techniques Haplotypes Humans Hydrolases - genetics Kinases Loci Male Medical research Middle Aged Osteoarthritis Pathogenesis Patients Peripheral blood Polymorphism, Single Nucleotide Protein-arginine deiminase Protein-Arginine Deiminases Proteins Rheumatoid arthritis Rheumatoid factor Risk factors Single nucleotide polymorphisms Single-nucleotide polymorphism Spondylitis Studies Synovial Membrane - metabolism Tissues |
| title | PADI2 is significantly associated with rheumatoid arthritis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-11T15%3A08%3A42IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=PADI2%20is%20significantly%20associated%20with%20rheumatoid%20arthritis&rft.jtitle=PloS%20one&rft.au=Chang,%20Xiaotian&rft.date=2013-12-05&rft.volume=8&rft.issue=12&rft.spage=e81259&rft.epage=e81259&rft.pages=e81259-e81259&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0081259&rft_dat=%3Cgale_plos_%3EA478419248%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1465243042&rft_id=info:pmid/24339914&rft_galeid=A478419248&rft_doaj_id=oai_doaj_org_article_ebfcafe500bb42728d013bd5334fafd1&rfr_iscdi=true |