Kretowski Adam, Mironczuk Katarzyna, Karpinska Anna, Bojaryn Urszula, Kinalski Maciej, Puchalski Zbigniew, Kinalska Ida
Department of Endocrinology, Diabetology and Internal Medicine, Academy of Bialystok, Bialystok, Poland.
Diabetes. 2002 Nov;51(11):3347-9. doi: 10.2337/diabetes.51.11.3347.
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.
1型糖尿病被认为是一种由Th1淋巴细胞介导的疾病，环境和遗传因素在其发病机制中均起作用。最近发现，白细胞介素（IL）-18作为一种促炎细胞因子，与IL-12协同作用，通过诱导γ-干扰素产生来促进Th1淋巴细胞反应的发展。由于最近报道在1型糖尿病亚临床阶段IL-18水平较高，我们研究的目的是评估1型糖尿病患者与健康对照者相比，IL-18启动子中已知多态性的频率。我们研究了IL-18基因启动子在-137和-607位置的两个最近描述的单核苷酸多态性，这两个多态性被认为会导致转录因子结合的差异并影响IL-18基因活性。1型糖尿病患者与对照者之间的基因型分布存在显著差异。这种差异反映了IL-18基因启动子-137位置GC基因型增加而GG基因型减少。-607位置的AA基因型仅在对照组中发现。结果还表明，-137GC基因型对1型糖尿病遗传易感性的贡献因IL-18启动子基因单倍型的组合而异。我们的研究首次表明1型糖尿病与IL-18基因启动子多态性之间存在关联。
