Association of CTLA-4 and CD28 Gene Polymorphisms with Type 1 Diabetes in South Indian Population

Nagarajan, Ganesh; Asirvatham, Arthur; Chitra, Ayyappan; Jayalakshmi, Mariakuttikan

doi:10.1080/08820139.2019.1590395

Cited by 9 publications

(3 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…9 Our study found that the frequency of G allele and GG homozygous genotype was significantly high in patients than in controls (p ¼ 0.01). This finding consistent with previous studies in populations from our continent includes Egyptians 16,18 and Tunisians, 19 together with other populations such as Indian, 20 Caucasian and Asian, 21,22 Iranians, [23][24][25] Estonian and Finnish, 26 Chilean, 27 and Russian. 28 Other studies among Sudanese, 9 Ghanaian, 29 and other populations, 30,31 did not prove this association.…”

Section: Discussionsupporting

confidence: 93%

CTLA-4 (+49A/G) Polymorphism in Type 1 Diabetes Children of Sudanese Population

Kheiralla

2021

Global Medical Genetics

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 93%

CTLA-4 (+49A/G) Polymorphism in Type 1 Diabetes Children of Sudanese Population

Kheiralla

2021

Global Medical Genetics

View full text Add to dashboard Cite

show abstract

Section: Introductionmentioning

confidence: 99%

“…11 In contrast, the CTLA-4 promoter −318 C/T polymorphism is associated with higher promoter activity, which increases CTLA-4 expression and thus decreases T-cell activity, and this polymorphism could be protective against the pathogenesis of autoimmune diseases. 12 In this study, we applied PCR-RFLP method 13 to detect the gene polymorphisms of promoter exon −318C/T and +49A/G of CTLA-4, and demonstrated the correlation between the gene polymorphisms of −318C/T and +49A/G of CTLA-4 and type 1 and 2 diabetes in Han population in northern China, which provides a new molecular epidemiological basis for the genetic study of diabetes and for predicting the development and genotyping of DM. Our data suggest that the CTLA-4 polymorphisms are important predictors of DM and CTLA-4 may be a susceptibility gene for type 2 diabetes.…”

Section: Introductionmentioning

confidence: 99%

Association of CLTA-4 Gene Polymorphisms with Diabetes Mellitus: A Study Based on the Han Population of Northern China

Ren¹,

He²,

Pang³

2022

DMSO

View full text Add to dashboard Cite

Objective This study aimed to investigate the association of CLTA-4 gene polymorphism with Type 1 and 2 diabetes mellitus (DM) (T1DM and T2DM) in the Han population of northern China. Methods A total of 234 Chinese Han DM patients and 187 non-diabetic subjects were included in the study. Two gene polymorphisms of the CLTA-4, including CTLA-4+49A/G (rs231775) and CTLA4-318C/T (rs5742909), were studied using polymerase chain reaction-restriction endonuclease fragment length polymorphism (PCR-RFLP) analysis. Chi-square analysis and Student’s t -test were performed to determine the distribution of the gene polymorphism and alleles at the locus of CTLA4-318C/T and CTLA4+49A/G among T1DM and T2DM patients with or without diabetic ketosis (DK), diabetic nephropathy (DN) or autoantibodies (Ab). Results Our results indicated that the distribution frequencies of genotypes and alleles at the CTLA-4+49A/G and CTLA4-318C/T loci of T1DM patients were not significantly different from those of the controls. However, the distribution frequencies of genotypes and alleles at the CTLA-4+49A/G loci of T2DM patients were significantly different from the controls (P=0.024 for genotypes and P=0.004 for A and G alleles). Besides, the A and G alleles at the CTLA4-318C/T loci of T2DM DK+ patients showed significantly different distribution frequencies compared to those of the T2DM DK patients (P=0.001). Conclusion Our data suggest that the gene polymorphisms of CTLA-4, including CTLA-4+49A/G and CTLA4-318C/T, are important predictors of DM. CTLA-4 may be a susceptibility gene for T2DM. Patients with T2DM carrying the T allele at the CTLA4-318 C/T locus are more predisposed to diabetic ketosis.

show abstract