Association of IL-18 promoter polymorphisms with predisposition to Type 1 diabetes.
OBJECTIVE
IL-18, a potent IFN-gamma-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 (pc = 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.
Department of Immunology, Shiraz University of Medical Sciences, Shiraz, Iran.
Z
Z
Mojtahedi
S
S
Naeimi
S
S
Farjadian
G R
GR
Omrani
A
A
Ghaderi
D000328:Adult; D017668:Age of Onset; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics*; D007492:Iran / Q000453:epidemiology; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*
D020382:Interleukin-18