{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:18:21Z","timestamp":1783487901188,"version":"3.55.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>Type 1 diabetes (T1D) is an increasingly complex disease influenced by both genetic and environmental triggers, leading to overactivity of the immune system. This preliminary study was conducted to investigate the association of two common cytotoxic T lymphocyte antigen-4 (CTLA-4) variants with T1D susceptibility in the Kurdish population of Iraq. Additionally, we evaluated the correlation between these polymorphisms and anti-GAD antibody positivity, as well as their possible influence on CTLA-4 gene expression. In this study, 52 patients (28 males and 24 females) with T1D and 21 healthy control subjects were genotyped for two (CTLA-4) SNPs, A&amp;gt;G (rs231775) and -318 C&amp;gt;T (rs5742909), using direct DNA sequencing. Furthermore, serum anti-GAD antibody levels were measured by ELISA technique, and the expression of CTLA-4 levels was assessed with quantitative real-time PCR. We discovered that the A&amp;gt;G (rs231775) variant was significantly associated with T1DM. The G allele frequency was significantly higher in type 1 diabetes patients (36.5%, P\u00a0=\u00a00.0188). The -318 C\/T polymorphism showed no significant differences between groups. The GG genotype of the +49A\/G polymorphism exhibited a greater prevalence in anti-GAD positive patients relative to negative individuals (77.78% vs. 22.22%), indicating an elevated risk trend (OR\u00a0=\u00a02.77, 95% CI: 0.51\u201314.91); however, this finding did not achieve statistical significance (P\u00a0=\u00a00.28). The (CTLA-4) mRNA gene expression was observed to be non-significantly elevated in T1D relative to the control group (p = 0.1239). Our data indicate that the G allele of the CTLA-4\u00a0+\u00a049 A&amp;gt;G variant is associated with increased T1D susceptibility in the Kurdish population, while the genotypic association showed a nominal trend.<\/jats:p>","DOI":"10.3389\/fendo.2026.1862007","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T04:52:01Z","timestamp":1783486321000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Association between CTLA-4 gene polymorphisms and Type 1 diabetes in Kurdish patients"],"prefix":"10.3389","volume":"17","author":[{"given":"Hero H. Muhammed","family":"Saed","sequence":"first","affiliation":[{"name":"Chemistry Department, College of Education, University of Garmian","place":["Kalar, Iraq"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaza F.","family":"Salih","sequence":"additional","affiliation":[{"name":"Biology Department, College of Science, University of Sualimani","place":["Slemani, Iraq"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassan Mohammad","family":"Tawfeeq","sequence":"additional","affiliation":[{"name":"Nursing Department, Kalar Technical Institute, Garmian Polytechnic University","place":["Kalar, Iraq"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1326711","article-title":"Immunological and virological triggers of type 1 diabetes: insights and implications","volume":"14","author":"Lemos","year":"2023","journal-title":"Front Immunol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s11892-020-01370-4","article-title":"The \u03b2 -cell genomic landscape in T1D\u00a0: implications for disease pathogenesis","volume":"21","author":"Ramos-Rodr\u00edguez","year":"2021"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/5.7.1075","article-title":"The CTLA-4 gene region of chromosome 2q33 is linked to, and associated with, type 1 diabetes","volume":"5","author":"Nistic\u00f2","year":"1996","journal-title":"Hum Mol Genet"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3390\/genes14040874","article-title":"Evidence of association between CTLA-4 gene polymorphisms and colorectal cancers in Saudi patients","volume":"14","author":"Al-Harbi","year":"2023","journal-title":"Genes (Bsl)"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.26.3.843","article-title":"Association of the CTLA-4 gene 49 A \/ G polymorphism with type 1 diabetes","volume":"26","author":"Anazawa","year":"2003","journal-title":"Diabetes Care"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M206894200","article-title":"A common autoimmunity predisposing signal peptide variant of the cytotoxic T-lymphocyte antigen 4 results in inefficient glycosylation of the susceptibility allele","volume":"277","author":"Anjos","year":"2002","journal-title":"J Biol Chem"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2009.03083.x","article-title":"The CTLA-4 gene polymorphisms are associated with CTLA-4 protein expression levels in multiple sclerosis patients and with susceptibility to disease","volume":"128","author":"Karabon","year":"2009","journal-title":"Immunology"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real- time quantitative PCR and the 2 \u03ea \u232c\u232c C T method","volume":"25","author":"Livak","year":"2023","journal-title":"METHODS"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3923\/pjbs.2013.1929.1935","article-title":"Association of CTLA-4 gene 49A\/G polymorphism with the incidence of type 1 diabetes mellitus in the Iranian\u00a0Kurdish population","volume":"16","author":"Ahmadi","year":"2013","journal-title":"Pak J Biol Sci"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.4103\/0971-6866.45001","article-title":"The CTLA4 -819 C \/ T and + 49 A \/ G dimorphisms are associated with type 1 diabetes in Egyptian children","volume":"14","author":"Saleh","year":"2008","journal-title":"Indian J Hum Genet"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1055\/s-0041-1723008","article-title":"CTLA-4 (+49A \/ G) polymorphism in type 1 diabetes children of Sudanese population","volume":"8","author":"Kheiralla","year":"2021","journal-title":"Glob Med Genet"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.2147\/DMSO.S375023","article-title":"Association of cytotoxic T-lymphocyte antigen-4 gene polymorphism with type 1 diabetes mellitus\u00a0: In silico analysis of biological features of CTLA-4 protein on Ethiopian population","volume":"15","author":"Ebrahim","year":"2022","journal-title":"Diabetes Metab Syndr Obes Targets Ther"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0039.2006.00745.x","article-title":"Insulin gene VNTR, CTLA-4 1 49A \/ G and HLA-DQB1 alleles distinguish latent autoimmune diabetes in adults from type 1 diabetes and from type 2 diabetes group","volume":"69","author":"Haller","year":"2007","journal-title":"Tissue Antigens"},{"key":"B14","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1046\/j.1365-2249.1997.5121410.x","article-title":"CTLA-4 gene polymorphism confers susceptibility to insulin-dependent diabetes mellitus (IDDM) independently from age and from other genetic or immune disease markers. 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