Aims IL-18, a potent IFN-γ-inducing cytokine, is capable of polarizing the immune response to a Th1 phenotype. Recent studies have demonstrated an association between single-nucleotide polymorphisms located at positions −607 (A/C) and −137 (C/G) in the promoter region of IL-18 gene and Type 1 diabetes. The aim of the present study was to determine whether the same polymorphisms of the gene were associated with Type 1 diabetes in Iranians.

Methods In 112 patients with Type 1 diabetes and 194 non-diabetic control subjects, these two single-nucleotide polymorphisms were analysed by sequence-specific PCR.

Results Allele and genotype frequencies of the IL-18 gene polymorphisms were similar in the whole group of Type 1 diabetic patients and controls. However, categorizing patients according to age at onset of diabetes revealed a significant difference in distribution of the genotypes at position −137 between patients with older age at onset (> 15 years) (GG 49%, GC 34%, CC 17%) and control subjects (GG 57.7%, GC 36.6%, CC 5.7%) (P = 0.027). Frequency of the C allele at position −137 was significantly higher in these patients than in controls (P = 0.038). Moreover, there was an association between −607AA/−137CC genotype combination and susceptibility to Type 1 diabetes in this subgroup of patients (p_c = 0.027).

Conclusions The results of this study show that polymorphisms of IL-18 promoter confer susceptibility to Type 1 diabetes in Iranian individuals with onset at older ages. Further investigations are necessary to clarify the effect of IL-18 variants on immune regulation.

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Volume23, Issue3

March 2006

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Association of IL-18 promoter polymorphisms with predisposition to Type 1 diabetes

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