{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:24:06Z","timestamp":1785435846647,"version":"3.56.0"},"reference-count":43,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T00:00:00Z","timestamp":1784332800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007051","name":"Uppsala University","doi-asserted-by":"publisher","award":["2346Bv"],"award-info":[{"award-number":["2346Bv"]}],"id":[{"id":"10.13039\/501100007051","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2346Bv"],"award-info":[{"award-number":["2346Bv"]}],"id":[{"id":"https:\/\/ror.org\/048a87296","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Rheumatoid arthritis (RA) is a chronic autoimmune disease marked by sustained synovial inflammation and systemic immune activation. Genetic polymorphisms in key immune-regulatory pathways are thought to influence both disease susceptibility and progression. This study aimed to characterize sequence variation within selected coding regions of TNFAIP3 and CTLA4 in Kurdish patients with RA and to evaluate circulating TNF-\u03b1 and soluble CTLA-4 (sCTLA-4) levels in the same cohort. Methods: Eighty-seven participants (67 RA patients, 20 controls) were enrolled. Serum TNF-\u03b1 and sCTLA-4 concentrations were quantified by ELISA. Genomic DNA was extracted and targeted Sanger sequencing of selected coding regions of TNFAIP3 and CTLA4 was performed in RA patients. Variant identification was conducted relative to GRCh38 and annotated using dbSNP and Genome Aggregation Database (gnomAD). GeneMANIA was used for network-based contextualization. Results: In the 218-bp targeted region of TNFAIP3, 103 sequence-level variant occurrences were identified in RA patients, including substitutions and insertion\/deletion events. In the 136-bp targeted region of CTLA4, 33 sequence-level variant occurrences were identified, also including substitutions and insertion\/deletion events. RA patients exhibited significantly elevated serum TNF-\u03b1 levels compared with controls (p = 0.025), whereas sCTLA-4 levels did not differ significantly. Conclusions: This study provides the first targeted characterization of TNFAIP3 and CTLA4 genetic variation in Kurdish RA patients and integrates these findings with circulating inflammatory biomarkers. Although not designed to assess disease susceptibility, the study provides a valuable descriptive genetic resource for this population and complements existing evidence implicating NF-\u03baB regulation and immune checkpoint signaling in RA. These findings establish a strong foundation for future case\u2013control, genotype\u2013phenotype, and functional investigations.<\/jats:p>","DOI":"10.3390\/genes17070821","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T12:00:17Z","timestamp":1784548817000},"page":"821","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic Variations in TNFAIP3 and CTLA4 and Their Association with Circulating TNF-\u03b1 and sCTLA4 Levels in Kurdish Patients with Rheumatoid Arthritis"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2188-9841","authenticated-orcid":false,"given":"Sonia Elia","family":"Ishaq","sequence":"first","affiliation":[{"name":"Department of Biology, College of Science, Salahaddin University-Erbil, Erbil 44001, Kurdistan Region, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9586-7843","authenticated-orcid":false,"given":"Taban Kamal","family":"Rasheed","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, Salahaddin University-Erbil, Erbil 44001, Kurdistan Region, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niaz","family":"Albarzinji","sequence":"additional","affiliation":[{"name":"College of Medicine, Hawler Medical University, Erbil 44001, Kurdistan Region, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shukur Wasman","family":"Smail","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Cihan University-Erbil, Erbil 44001, Kurdistan Region, Iraq"},{"name":"Department of Medical Science, Respiratory Medicine, and Allergology, Respiratory Allergy and Sleep Research, Uppsala University and University Hospital, 75185 Uppsala, Sweden"},{"name":"Department of Genetics, Bio Diagnostic Center (BDC), Erbil 44001, Kurdistan Region, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e594","DOI":"10.1016\/S2665-9913(23)00211-4","article-title":"Global, regional, and national burden of rheumatoid arthritis, 1990\u20132020, and projections to 2050: A systematic analysis of the Global Burden of Disease Study 2021","volume":"5","author":"Collaborators","year":"2023","journal-title":"Lancet Rheumatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1002\/1529-0131(200001)43:1<30::AID-ANR5>3.0.CO;2-B","article-title":"Characterizing the quantitative genetic contribution to rheumatoid arthritis using data from twins","volume":"43","author":"MacGregor","year":"2000","journal-title":"Arthritis Rheum."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.cellimm.2014.05.003","article-title":"Protein tyrosine phosphatase non-receptor type 22 (PTPN22) +1858 C>T gene polymorphism in Egyptian cases with rheumatoid arthritis","volume":"290","author":"Salama","year":"2014","journal-title":"Cell. 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