https://orcid.org/0000-0002-5306-6658
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Abstract
Background
T1DM is a chronic organ-specific T-cell-mediated autoimmune disease characterized by the selective destruction of β-cells in the islets of Langerhans, resulting in insulin deficiency and hyperglycemia. Genes for cytotoxic T lymphocyte-associated antigen 4 have been hypothesized as possible contender genes for T1DM vulnerability. However, it has not been studied in the Ethiopian population yet.
Objective
The aim of the study was to investigate CTLA-4 exon 1 was linked to A49G polymorphism with T1DM and its biological features of CTLA-4 among T1DM patients, in Ethiopia.
Methods
A case–control study was done from December 2019 to March 2020 on 210 study participants (105 T1DM patients and 105 healthy controls). Polymerase Chain Reaction amplification with forward and reverse primers was followed by restriction fragment length polymorphism and gel electrophoresis to determine gene polymorphism. Bioinformatics data of SNP was retrieved from National Centers for Biotechnology Information databases. The chi-square test and logistic regression were used. Statistical significance was defined as a P-value of less than 0.05.
Results
The CTLA-4 (+A49G) gene polymorphism was observed on 56 (26.7%) study participants, 39 (18.57%) of T1DM patients, and 17 (0.08%) were controls. In T1DM and controls, the frequency of the A allele was 73.3% and 89.5%, while the G allele was 26.7% and 10.5%, respectively. The G allele was found to be associated with T1DM (OR=3.1; 95% CI, 1.82 −5.32; P=0.001). Statistical analysis revealed an association between the likelihood of T1DM and GG genotype of the CTLA-4 (+A49G) gene polymorphism (OR=3.11; 95% CI, 1.37–10.90; P=0.01). Further in silico analyzed the SNP to assess its biological features.
Conclusion
The study showed as CTLA-4 (+A49G) gene polymorphism is linked with T1DM in the Ethiopian population.
Keywords:
Abbreviations
A, adenine; CI, confidence interval; CTLA-4, cytotoxic T-lymphocyte-associated antigen 4; DKA, diabetic keto acidosis; DM, diabetes mellitus; DNA, deoxyribonucleic acid; G, guanine; HIC, high-income countries; HLA, human leukocyte antigen; IDDM, insulin-dependent diabetes mellitus; LADA, latent auto-immune diabetes in adults; LMIC, low middle-income countries; RFLP, restriction fragment length polymorphism; RT-PCR, real-time polymerase chain reaction; SNP, single nucleotide polymorphism; T1DM, type 1 diabetes mellitus.
Data Sharing Statement
All the relevant data are within the manuscript.
Acknowledgment
The authors thank the University of Gondar for its approval and facilitation of the work. In addition, the authors would like to thank the University of Gondar and Wollo University for their financial assistance and sponsorship of successful research opportunities. Any attempt at any level cannot be completed satisfactorily without the support and guidance of Abubeker Alebachew, which assists me with the progression of this research work.
The authors would like to thank Prof. Manuel Lemos (CICS-UBI, Health Sciences Research Centre, University of Beira Interior, Portugal) for providing the genotyping primers. Finally, I could not have completed this project without the help of my classmates, data collectors, study participants, and all of my friends, staff, and Hospital communities who helped me a lot in gathering different information, collecting data, and guiding me from time to time in making this project, despite their busy schedules, they gave me different ideas in making this project successful.
Disclosure
The authors declare that no commercial or financial relationships that could be construed as a potential conflict of interest existed during the research.