Association study of IL2RA and CTLA4 Gene Variants with Type I Diabetes Mellitus in children in the northwest of Iran Association study of IL2RA and CTLA4 gene variants with type-1 diabetes mellitus in children in the northwest of Iran

Abstract

Introduction: A variety of genetic predisposing factors and environmental factors are known to influence the pathogenesis of type-1 diabetes (T1D). This study intended to investigate the association of cytotoxic T-lymphocyte associated protein 4 (CTLA4) and interleukin 2 receptor subunit alpha (IL2RA) gene polymorphisms with type 1 diabetes in children of northwest of Iran. Methods: Genomic DNA was extracted by salting-out method. PCR amplification and direct sequencing methods were used for genotyping of CTLA4 (exon 1) and IL2RA (intron 1) genes in all patients and controls. SNPStats was used to calculate odds ratios (ORs), 95% confidence intervals (CIs), and p values. Results: In this study, the frequency of G allele and GG genotype of CTLA-4 (+49A/G) polymorphism in T1D patients were significantly different from those in the controls (26% vs. 11%, p = 0.006). Moreover, a significant difference was observed between patients and control group in the allele frequencies of the new SNP (chr2:203868145) that was identified in exon one of CTLA4 (14% vs. 3%, p = 0.006). The results showed that the GG homozygous genotype of +49 A>G was associated with increased glycemic level in T1D patients in the study population (95% CI = 10.47, p = 0.0067). However, no significant association was found between IL2RA (ss52580101C>A) polymorphism and T1D patients (2% vs. 4%, p = 0.41). Conclusion: The results further support the association of T1D with +49A>G SNP in the CTLA4 gene in the population of northwest of Iran. However, no significant relationship was observed between ss52580101C>A polymorphism of IL2RA gene and T1D in this study.

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

“…Our study found that the frequency of G allele and GG homozygous genotype was significantly high in patients than in controls ( p = 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.…”

“…We studied the CTLA-4 (+49 A/G) polymorphism because it has been the most widely analyzed variant in different ethnic groups, and still with inconsistent findings. 16 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 Furthermore, this is the first study investigated the effect of +49A/G polymorphism among Sudanese children with T1DM, bearing in mind a recent data investigated this polymorphism among Sudanese adults with T1DM. 9 …”

Imunologia do Diabetes Mellitus do tipo 1 e vias de glico-oxidação relacionadas a hiperglicemia

“…Alterações genéticas, principalmente na região do complexo maior de histocompatibilidade (MHC). Além do MHC, outros genes possuem relação com o desenvolvimento deste distúrbio, como polimorfismos nos genes que codificam a insulina (INS), CTLA4, PTPN2 e IL2RA que possuem maior chance de mutação em populações específicas como asiáticos e causasianos (Ikegami et al, 2008;Ranjouri et al, 2016;Van Belle et al, 2011).…”

Juxtaposition of Coeliac Disease and Type 1 Diabetes; the Role of Shared Non-Human Leukocyte Antigen Loci

“…46,47 Multiple studies have noted predisposing role for minor G allele of this polymorphism for CD 18 and T1D. [13][14][15][19][20][21][22][23][24] Two studies; Mora et al, Naluai et al 16,17 have observed the higher risk of CD in individuals bearing the wild-type A allele of this polymorphism. On the other hand, some have not reported any significant association between this polymorphism with the occurrence of CD 12,13 and T1D.…”