{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T21:14:54Z","timestamp":1762809294665,"version":"3.40.5"},"reference-count":41,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T00:00:00Z","timestamp":1654214400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["33\/6\/2019TF\/Rare\/BMS"],"award-info":[{"award-number":["33\/6\/2019TF\/Rare\/BMS"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J of Rheum Dis"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Granulomatosis with polyangiitis (GPA) is a rare systemic autoimmune disease. Smaller sample size and complex nature of the disease pathogenesis has made it challenging to perform well\u2010powered genetic investigations. We performed a systematic review based meta\u2010analysis in GPA to investigate the genetic susceptibility conferred by non\u2010human leukocyte antigen (non\u2010HLA) candidate genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A systematic review was performed using web\u2010based literature search and eligible studies were included following inclusion\u2010exclusion criteria. Studies were evaluated for their quality of evidence and study outcome was assessed using the Newcastle\u2010Ottawa Scale and Grades of Research, Assessment, Development and Evaluation tools. Reviewer's agreement was accessed through Cohen's \u03ba value. Meta\u2010analyses were performed using RevMan 5 tool. Meta\u2010odds ratio (meta\u2010OR) and Z test <jats:italic>P<\/jats:italic> value were evaluated to estimate the genetic susceptibility for each of the variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Eighteen studies were found eligible and 7 genetic variants from only 4 genes, namely <jats:italic>CTLA4<\/jats:italic>, <jats:italic>PRTN3<\/jats:italic>, <jats:italic>SERPINA1<\/jats:italic> and <jats:italic>PTPN22<\/jats:italic> could be studied for meta\u2010analysis. rs231775\u2010G (49\u2010G) (Meta\u2010OR\u00a0=\u00a01.42 [1.14\u20101.76]; <jats:italic>P<\/jats:italic>\u00a0=\u00a0.001) of <jats:italic>CTLA4<\/jats:italic> and rs7151526\u2010A (Meta\u2010OR\u00a0=\u00a02.70 [1.51\u20104.85]; <jats:italic>P<\/jats:italic>\u00a0=\u00a0.0008) of <jats:italic>SERPINA1<\/jats:italic> were confirmed to be predisposing alleles, and rs5742909\u2010C (318\u2010C) (Meta\u2010OR\u00a0=\u00a00.65 [0.44\u20100.97]; <jats:italic>P<\/jats:italic>\u00a0=.03) of <jats:italic>CTLA4<\/jats:italic> was found to be protective for GPA. In concordance with the genetic association of rs7151526\u2010A, serological marker for the same variant \u201cZ\u201d allele of <jats:italic>SERPINA1<\/jats:italic> was found to be predisposing (Meta\u2010OR\u00a0=\u00a012.60 [5.01\u201031.68]; <jats:italic>P<\/jats:italic>\u2009&lt;\u2009.00001) for GPA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Genetic variants confirmed in this study play critical roles in T\u2010cell mediated immune function and could be significantly implicated in GPA. Molecular pathology studies are warranted to confirm their role. These markers could be used for efficient patient classification and disease management.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1756-185x.14354","type":"journal-article","created":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T09:28:56Z","timestamp":1654248536000},"page":"811-819","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Meta\u2010analysis confirmed genetic susceptibility conferred by multiple risk variants from <scp>CTLA4<\/scp> and <scp>SERPINA1<\/scp> in granulomatosis with polyangiitis"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9534-4425","authenticated-orcid":false,"given":"Pratibha","family":"Banerjee","sequence":"first","affiliation":[{"name":"Immunogenomics Laboratory, Department of Human Genetics &amp; Molecular Medicine, School of Health Sciences Central University of Punjab  Ghudda Punjab India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3281-7683","authenticated-orcid":false,"given":"Uma","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Rheumatology All India Institute of Medical Sciences  New Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0510-3370","authenticated-orcid":false,"given":"Preeti","family":"Khetarpal","sequence":"additional","affiliation":[{"name":"Laboratory for Reproductive and Developmental Disorders, Department of Human Genetics &amp; Molecular Medicine, School of Health Sciences Central University of Punjab  Ghudda Punjab India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9448-7432","authenticated-orcid":false,"given":"Sabyasachi","family":"Senapati","sequence":"additional","affiliation":[{"name":"Immunogenomics Laboratory, Department of Human Genetics &amp; Molecular Medicine, School of Health Sciences Central University of Punjab  Ghudda Punjab India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,6,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.7861\/clinmedicine.17-1-60"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-021-05011-1"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1108735"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcp.2016.08.009"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1993.186"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40034"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003585"},{"issue":"1","key":"e_1_2_9_9_1","first-page":"1","article-title":"Confirmation of the genetic association of CTLA4 and PTPN22 with ANCA\u2010associated vasculitis","volume":"10","author":"Carr EJ","year":"2009","journal-title":"BMC Med Genet"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.34496"},{"issue":"8","key":"e_1_2_9_11_1","first-page":"e17103","article-title":"The co\u2010existence of rheumatoid arthritis and granulomatosis with polyangiitis: two cases and review of the literature","volume":"13","author":"Hassan AS","year":"2021","journal-title":"Cureus"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41435-021-00123-x"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38036"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2008.03.506"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.20385"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/1756-185X.13837"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2000.00430.x"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1744-313X.2005.00519.x"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1000097"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.2307\/2529310"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00383-018-4358-6"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2010.07.015"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0197-2456(86)90046-2"},{"issue":"5","key":"e_1_2_9_24_1","first-page":"950","article-title":"Coding sequence 1 and promoter single nucleotide polymorphisms in the CTLA\u20104 gene in Wegener's granulomatosis","volume":"29","author":"Giscombe R","year":"2002","journal-title":"J Rheumatol"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kep280"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1159\/000355744"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2362.1997.1720717.x"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27742"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1042\/cs0870693"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.1995.tb03652.x"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2362.1996.2070553.x"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.ndt.a027308"},{"issue":"3","key":"e_1_2_9_33_1","first-page":"206","article-title":"Alpha\u20101\u2010antitrypsin phenotyping in ANCA\u2010associated diseases: one of several arguments for protease\/antiprotease imbalance in systemic vasculitis","volume":"14","author":"Esnault VL","year":"1997","journal-title":"Exp Clin Immunogenet"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ker446"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6966"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2436-0"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12760"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.06.013"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gene.6363869"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204164"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/5584_2018_156"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.180591"}],"container-title":["International Journal of Rheumatic Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1756-185X.14354","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/1756-185X.14354","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1756-185X.14354","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T02:27:13Z","timestamp":1692844033000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1756-185X.14354"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,3]]},"references-count":41,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2022,7]]}},"alternative-id":["10.1111\/1756-185X.14354"],"URL":"https:\/\/doi.org\/10.1111\/1756-185x.14354","archive":["Portico"],"relation":{},"ISSN":["1756-1841","1756-185X"],"issn-type":[{"type":"print","value":"1756-1841"},{"type":"electronic","value":"1756-185X"}],"subject":[],"published":{"date-parts":[[2022,6,3]]},"assertion":[{"value":"2021-09-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}