Abstract
Background Type 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. Aims This study aimed to investigate the association of CTLA-4 +49A/G (rs231775) polymorphism with a risk of T1DM in Sudanese children. Methods This a case–control 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. Results The genotype and allele frequencies of the CTLA-4 (+49A/G) polymorphism were significantly different between the patients and controls ( p = 0.00013 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) = 5.16, 95% confidence interval [CI] = 2.77–9.65, p = 0.00] [12% versus 2%, OR = 6.68, CI = 1.46–30.69, p = 0.01] [32% versus 10%, OR = 4.24, CI = 1.95–9.21, p = 0.00], respectively). The presence of the G allele (homozygous) showed an influence on the signal peptide polarity, hydrophobicity, and α-helix propensity of the CTLA-protein. Conclusion The results further support the association of CTLA-4 (+49A/G) polymorphism and the risk of T1DM in our study population.
Highlights
Type 1 diabetes mellitus (T1DM) is an organ-specific and T cell-mediated autoimmune disease primarily affects children and adolescents
This study aimed to investigate the association of Cytotoxic lymphocyte antigen-4 (CTLA-4) þ49A/G polymorphism with a risk of T1DM in Sudanese children
The genotype and allele frequencies of the CTLA-4 (þ49A/G) polymorphism were significantly different between the patients and controls (p 1⁄4 0.00013 and 0.0002, respectively)
Summary
Type 1 diabetes mellitus (T1DM) is an organ-specific and T cell-mediated autoimmune disease primarily affects children and adolescents. 12 CTLA-4 Polymorphism Susceptibility Kheiralla associated with susceptibilities to a wide range of T cellmediated autoimmune diseases.[3]. One of these polymorphisms was the CTLA-4 þ49A/G single nucleotide polymorphism (SNP) that causes a threonine-to-alanine substitution in codon 17, which altered protein expression[4] and T cell activation.[5] Since the þ49A/G SNP is located in the N-terminal of the signal peptide sequence of the CTLA-4, which is not a part of the mature protein, the substitution of threonine to alanine may affect the proper translocation of the growing CTLA-4 peptide from ribosome to endoplasmic reticulum (ER) lumen, as a result of alteration in signal peptide hydrophobicity and helix propensity,[6] rendered possible evidence of defective CTLA-4 targeting to the cell surface.[7]. The changes accompanied the polymorphism were evaluated using relevant bioinformatics tools
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
