Interleukin-18 promoter polymorphisms in type 1 diabetes.
Type 1 diabetes is believed to be a Th1 lymphocyte-mediated disease, and both environmental and genetic factors play a role in its pathogenesis. It was recently found that interleukin (IL)-18 acts as a proinflammatory cytokine and, in synergy with IL-12, promotes development of Th1 lymphocyte response by induction of gamma-interferon production. The aim of our study was to evaluate the frequency of known polymorphisms in the IL-18 promoter in patients with type 1 diabetes in comparison with healthy control subjects, since higher levels of IL-18 were recently reported in the subclinical stage of type 1 diabetes. We studied two recently described single-nucleotide polymorphisms of the promoter of IL-18 gene at the position -137 and -607, which have been suggested to cause differences in transcription factor binding and have an impact on IL-18 gene activity. The genotype distribution differed significantly between patients with type 1 diabetes and control subjects. The difference reflected an increase in the GC genotypes and a decrease in GG genotypes at position -137 in the promoter of IL-18 gene. AA genotype at position -607 was found only in the control group. The results also demonstrated that the contribution of -137GC genotypes to genetic susceptibility to type 1 diabetes differs depending on the combination of IL-18 promotor gene haplotypes. Our study suggests the first evidence of an association between type 1 diabetes and polymorphisms in the promoter of IL-18 gene.
Kretowski
Adam
A
Department of Endocrinology, Diabetology and Internal Medicine, Academy of Bialystok, Bialystok, Poland. akretows@amb.ac.bialystok.pl
Mironczuk
Katarzyna
K
Karpinska
Anna
A
Bojaryn
Urszula
U
Kinalski
Maciej
M
Puchalski
Zbigniew
Z
Kinalska
Ida
I
D001483:Base Sequence; D017931:DNA Primers; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D006239:Haplotypes; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012016:Reference Values; D018417:Th1 Cells / Q000276:immunology
D017931:DNA Primers; D020382:Interleukin-18