{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:52:19Z","timestamp":1787014339024,"version":"build-2736575974"},"reference-count":44,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002383","name":"King Saud University","doi-asserted-by":"publisher","award":["ORF\u20102025\u2010339"],"award-info":[{"award-number":["ORF\u20102025\u2010339"]}],"id":[{"id":"10.13039\/501100002383","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J Immunogenetics"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The main objective of the study was to determine the association of genes\n                    <jats:italic>AIRE<\/jats:italic>\n                    (rs2075876),\n                    <jats:italic>CD40<\/jats:italic>\n                    (rs4810485),\n                    <jats:italic>HLA\u2010DRB1<\/jats:italic>\n                    (rs6457617) and\n                    <jats:italic>TRAF1\/C5<\/jats:italic>\n                    (rs10818488) polymorphisms with rheumatoid arthritis (RA) from the population of Pakistan. Blood samples of 300 RA patients and 300 healthy controls were taken from different hospitals in Pakistan. Extraction of DNA was carried out; a specific region of DNA was amplified using PCR. Polymorphic analysis was performed for genes\n                    <jats:italic>AIRE<\/jats:italic>\n                    (rs2075876),\n                    <jats:italic>CD40<\/jats:italic>\n                    (rs4810485),\n                    <jats:italic>HLA\u2010DRB1<\/jats:italic>\n                    (rs6457617) and\n                    <jats:italic>TRAF1\/C5<\/jats:italic>\n                    (rs10818488). The demographic parameters, like age, showed statistically significant association and increased the risk of the disease up to 2\u2010fold (odds ratio [OR]\u00a0=\u00a02.57; 95% confidence interval [CI]\u00a0=\u00a01.60\u20134.12;\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.0001). Gender and family history did not show any significant association with arthritis (OR\u00a0=\u00a01.12; 95% CI\u00a0=\u00a00.69\u20131.81;\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.6260; OR\u00a0=\u00a00.70; 95% CI\u00a0=\u00a00.44\u20131.11;\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.1313, respectively). In the case of smoking status, the difference was statistically significant for both smokers and non\u2010smokers. In smokers, there was a decreased risk of RA (OR\u00a0=\u00a00.45; 95% CI\u00a0=\u00a00.28\u20130.73;\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.0011), and in non\u2010smokers, there was an increased risk of disease up to 2\u2010fold (OR\u00a0=\u00a02.17; 95% CI\u00a0=\u00a01.36\u20133.47;\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.0011). In\n                    <jats:italic>AIRE<\/jats:italic>\n                    gene, heterozygous (AG) of rs2075876 showed a highly significant association with increased risk of RA up to 3\u2010fold (OR\u00a0=\u00a03.39; 95% CI\u00a0=\u00a02.08\u20135.54;\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.0001), whereas homozygous mutant (GG) also showed significant association (OR\u00a0=\u00a00.43; 95% CI\u00a0=\u00a00.26\u20130.72;\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.0014) but with decreased risk. In\n                    <jats:italic>CD40<\/jats:italic>\n                    gene, heterozygous (AG) of rs4810485 showed significant association with a decreased risk of RA (OR\u00a0=\u00a00.59; 95% CI\u00a0=\u00a00.377\u20130.945;\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.027), whereas the homozygous mutant (GG) of rs4810485 showed highly significant association by increasing risk of up to 4\u2010fold (OR\u00a0=\u00a04.318; 95% CI\u00a0=\u00a02.553\u20137.303;\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.0001). In\n                    <jats:italic>HLA\u2010DRB1<\/jats:italic>\n                    gene, heterozygous (CT) of rs6457617 showed significant association with a decreased risk of disease (OR\u00a0=\u00a00.52; 95% CI\u00a0=\u00a00.35\u20130.85;\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.007), whereas the homozygous mutant (TT) of rs6457617 showed highly significant association by increasing the risk of RA up to 4\u2010fold (OR\u00a0=\u00a04.37; 95% CI\u00a0=\u00a02.55\u20137.47;\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.0001). In the\n                    <jats:italic>TRAF1\/C5<\/jats:italic>\n                    gene, heterozygosity (AG) of rs10818488 showed a significant association with an increased risk of disease up to 4\u2010fold (OR\u00a0=\u00a04.06; 95% CI\u00a0=\u00a02.38\u20136.98;\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.0001). Highly significant associations of genes\n                    <jats:italic>AIRE<\/jats:italic>\n                    (rs2075876),\n                    <jats:italic>CD40<\/jats:italic>\n                    (rs4810485),\n                    <jats:italic>HLA\u2010DRB1<\/jats:italic>\n                    (rs6457617) and\n                    <jats:italic>TRAF1\/C5<\/jats:italic>\n                    (rs10818488) polymorphisms were observed with RA.\n                  <\/jats:p>","DOI":"10.1111\/iji.70007","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T06:14:42Z","timestamp":1753251282000},"page":"262-273","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Polymorphism Analysis as Biomarker in Genes\n                    <i>AIRE<\/i>\n                    ,\n                    <i>CD40<\/i>\n                    ,\n                    <i>HLA\u2010DRB1<\/i>\n                    and\n                    <i>TRAF1\/C5<\/i>\n                    SNPs in Rheumatoid Arthritis Patients"],"prefix":"10.1111","volume":"52","author":[{"given":"Yalong","family":"Liu","sequence":"first","affiliation":[{"name":"Orthopedics Department 3 Heilongjiang Beidahuang Group General Hospital  Harbin City Heilongjiang Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayesha","family":"Chaudhary","sequence":"additional","affiliation":[{"name":"Department of Zoology University of Sargodha  Sargodha Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanza","family":"Quddus","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Superior University Lahore  Lahore Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehwish","family":"Aslam","sequence":"additional","affiliation":[{"name":"Department of Zoology University of Sargodha  Sargodha Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anisa","family":"Iftikhar","sequence":"additional","affiliation":[{"name":"Department of Biology Clarkson University  Potsdam New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azmat Ali","family":"Khan","sequence":"additional","affiliation":[{"name":"Pharmaceutical Biotechnology Laboratory, Department of Pharmaceutical Chemistry, College of Pharmacy King Saud University  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amer M.","family":"Alanazi","sequence":"additional","affiliation":[{"name":"Pharmaceutical Biotechnology Laboratory, Department of Pharmaceutical Chemistry, College of Pharmacy King Saud University  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kashif","family":"Bashir","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Superior University Lahore  Lahore Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,22]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.27860"},{"issue":"371","key":"e_1_2_12_3_1","first-page":"2167","article-title":"Review Article\u2010Comorbidities in Rheumatoid Arthritis","volume":"5","author":"Aziz M.","year":"2019","journal-title":"Journal of Nursing Care"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24054901"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1201\/9781003207160-13"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0199007"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2009.00859.x"},{"issue":"1","key":"e_1_2_12_8_1","first-page":"1","article-title":"Rheumatoid Synovial Fibroblasts Differentiate Into Distinct Subsets in the Presence of Cytokines and Cartilage","volume":"18","author":"Croft A. 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