{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T20:24:39Z","timestamp":1787862279722,"version":"build-2784847793"},"reference-count":42,"publisher":"Elsevier BV","issue":"01","license":[{"start":{"date-parts":[[2021,2,15]],"date-time":"2021-02-15T00:00:00Z","timestamp":1613347200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Global Medical Genetics"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\n          Background\u2003Type 1 diabetes mellitus (T1DM) is an organ-specific T cell-mediated autoimmune disease, characterized by destruction of pancreatic islets. Cytotoxic lymphocyte antigen-4 (CTLA-4) is a negative regulator of T cell proliferation, thus conferring susceptibility to autoimmunity.<\/jats:p><jats:p>\n          Aims\u2003This study aimed to investigate the association of CTLA-4 +49A\/G (rs231775) polymorphism with a risk of T1DM in Sudanese children.<\/jats:p><jats:p>\n          Methods\u2003This a case\u2013control study included 100 children with T1DM, referred to the pediatric clinic at referral pediatric teaching hospital in Gezira State-Sudan. Hundred unrelated healthy controls were recruited from departments in the same hospital. Genomic deoxyribonucleic acid (DNA) was extracted from Ethylenediaminetetraacetic Acid (EDTA)-preserved blood using QIAamp DNA Blood Mini Kit (QIAamp Blood) (QIAGEN; Valencia, CA). The polymerase chain reaction PCR restriction fragment length polymorphism (PCR-RFLP) and sequencing were applied for the CTLA-4 (+49A\/G) genotyping. The changes accompanied the polymorphism were evaluated using relevant bioinformatics tools.<\/jats:p><jats:p>\n          Results\u2003The genotype and allele frequencies of the CTLA-4 (+49A\/G) polymorphism were significantly different between the patients and controls (p\u2009=\u20090.00013 and 0.0002, respectively). In particular, the frequency of the G allele, GG homozygous genotype, and AG heterozygous genotype were significantly increased in patients than in controls ([28% versus 7%, odds ratio (OR)\u2009=\u20095.16, 95% confidence interval [CI]\u2009=\u20092.77\u20139.65, p\u2009=\u20090.00] [12% versus 2%, OR\u2009=\u20096.68, CI\u2009=\u20091.46\u201330.69, p\u2009=\u20090.01] [32% versus 10%, OR\u2009=\u20094.24, CI\u2009=\u20091.95\u20139.21, p\u2009=\u20090.00], respectively). The presence of the G allele (homozygous) showed an influence on the signal peptide polarity, hydrophobicity, and \u03b1-helix propensity of the CTLA-protein.<\/jats:p><jats:p>\n          Conclusion\u2003The results further support the association of CTLA-4 (+49A\/G) polymorphism and the risk of T1DM in our study population.<\/jats:p>","DOI":"10.1055\/s-0041-1723008","type":"journal-article","created":{"date-parts":[[2021,2,17]],"date-time":"2021-02-17T02:06:30Z","timestamp":1613527590000},"page":"011-018","source":"Crossref","is-referenced-by-count":17,"title":["CTLA-4 (+49A\/G) Polymorphism in Type 1 Diabetes Children of Sudanese Population"],"prefix":"10.1016","volume":"08","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9710-7477","authenticated-orcid":false,"given":"Khalid E.","family":"Khalid Kheiralla","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, Faculty of Applied Medical Sciences, Albaha University, Al Bahah, Saudi Arabia"},{"name":"Department of Biochemistry and Nutrition, Faculty of Medicine, University of Gezira, Wad Madani, Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","published-online":{"date-parts":[[2021,2,15]]},"reference":[{"issue":"11","key":"ref1","doi-asserted-by":"crossref","first-page":"6284","DOI":"10.1073\/pnas.95.11.6284","article-title":"B7-CTLA4 interaction enhances both production of antitumor cytotoxic T lymphocytes and resistance to tumor challenge","volume":"95","author":"P Zheng","year":"1998","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"03","key":"ref2","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1084\/jem.174.3.561","article-title":"CTLA-4 is a second receptor for the B cell activation antigen B7","volume":"174","author":"P S Linsley","year":"1991","journal-title":"J Exp Med"},{"issue":"01","key":"ref3","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1046\/j.0300-9475.2001.01019.x","article-title":"Expression 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