Association of cytotoxic T lymphocyte antigen 4 gene polymorphism with type 1 diabetes in children

Abstract EN

-Background: Type-1 diabetes mellitus (T1DM) is an autoimmune disease in which combinations of environmental and genetic factors contribute to T-cell mediated destruction of insulin- secreting T- cells of the pancreas.

The (CTLA- 4) encodes of the T-cell receptor involved in the control of T-cell proliferation.

Aim! The aim of this study was to investigate the association of CTLA- 4 gene exon 1 49 A/G polymorphism with T1DM in children and its relation to diabetic complications.

-Subjects and methods: A total of 100 subjects were included in this cross sectional, case- control study.

Fifty children with T1DM aged (JO- 18) years (12.5+ 2.0) years, and fifty children as a control group.

All candidates were subjected to full clinical evaluation and anthropometric measurements.

All the patients had the following laboratory investigation been done (RBG, average HbAlc, Quantitative determination of urinary microalbumin).

CTLA- 4 gene polymotphism PCR- RFLP was done for all the subjects.

-Results: CTLA- 4 genotyping among the diabetic group was: the mutant homozygous genotype GO in 15 (30%), the mutant heterozygous genotype AG in 29 (58%) and wild homozygous genotype AA in 6 (12%).

However, among the control group: it was 3 (6%) with GG genotype, 19 (38%) with AG genotype and 28 (56%) with AA genotype with P value <0.001 which denoting a higher prevalence of AG and GG genotype in diabetic group with highly statistical significance.

There was a significant association between CTLA- 4 mutant genotypes and patients with younger age of onset of diabetes (P= 0.011) and higher dose of insulin (P= 0.002).

CTLA- 4 +49 mutant genes did not have any impact on complications of type I diabetes.

-Conclusion: The results of the present study shows that the CTLA- 4 A/G +49 polymorphism was associated with type 1 diabetes in Egyptian children with a significant association between CTLA- 4 mutant genotypes and patients with younger age of onset of diabetes and higher dose of insulin.