Tehran University Medical Journal

Background: Type I diabetes is an autoimmune disease characterized by T-cell Mediated destruction of pancreatic β-cells. A variety of environmental, genetic and Immunologic factors are involved in the development of the disease. IL₁₈ is a cytokine secreted by macrophage and monocytes and play an important role in the pathogenesis of diabetes Type I through inducing IFN-γ production. It is shown to be strongly associated with the development of diabetes in NOD mice. It is also shown to have increased level in the subclinical stage of diabetes mellitus (type 1). Genetic polymorphisms in the IL-18 gene influence production and secretion of cytokine and are considered as a risk factor in auto-Immune diseases.

Methods: In this case control study, 75 type I diabetic patients and 88 healthy controls studied for polymorphism at positions -137 and -607. DNA extraction from the whole blood was performed according to the standardized method and polymorphism was determines by SSP-PCR. Data were analyzed by SPSS-12 using Chi-Square Test with 95% Confidence interval.

Results: A statistical significant difference in GG genotype (53%) and CC genotype (16%) at the -137 position of IL₁₈ gene was found, as compared to the control subjects (p=0.000) whereas we have not shown any statistical significance at the position -607.

Conclusion: IL₁₈ is a key cytokine secreted by macrophages and monocytes and stimulate the Th₁ lymphocyte. This cytokine can activate cytotoxic T lymphocytes (CTL) and destroy the pancreatic β cell. Our results show that the frequency of GG and CC genotypes at the position -137 may be associated with susceptibility to diabetes.