Medknow Publications on behalf of Indian Society of Human Genetics
Abstract
Background: Type 1 diabetes (T1D) is an organ-specific autoimmune
disease characterized by T cell-mediated destruction of pancreatic
islets. T cell proliferation is negatively regulated by cytotoxic
lymphocyte antigen-4 (CTLA-4). CTLA-4 polymorphisms are associated with
T1D in some but not all populations. Aims: The study was conducted to
investigate the association of the C-819T and A+49G single nucleotide
polymorphisms (SNP) of CTLA-4 gene in T1D patients in the Egyptian
population. Methods: The association of the C-819T SNP in intron 1 and
A+49G SNP in exon 1 of the CTLA-4 gene with T1D were investigated in
396 Egyptian patients ≤14 years old and 396 control subjects>
24 years old, with the same ratio of males to females in both groups.
The diagnosis of T1D was made on the basis of ketoacidosis or ketosis
with severe symptoms of acute onset at presentation and continuous
dependence on insulin. Controls were negative for anti-GAD antibodies
and were greater than 24 years of age. Genotyping was performed using
single strand conformation polymorphism (SSCP), temperature gradient
gel electrophoresis (TGGE), and polymerase chain reaction-restriction
fragment length polymorphism (PCR-RFLP). Results: The results
demonstrated an association of the C-819T and A+49G SNPs in the CTLA-4
gene with T1D patients (P=0.0047) and (P=0.000575), respectively.
Moreover, this association was stratified by gender and age to female
patients with age at onset 0-5 years old (P=0.0186) and (P=0.00115)
more than male patient with the age at onset 0-5 years old (P= 0.3120)
and (P=0.345161), respectively. Conclusion: The results support an
association of the C-819T and A+49G SNPs in the CTLA-4 gene with
Egyptian children, specifically, females of onset age 0-5 years old