Laboratório de Carboidratos e Radioimunoensaios (LIM/18) - Faculdade de Medicina da Universidade de São Paulo SP, Brazil.
Cytokine. 2013 Feb;61(2):349-52. doi: 10.1016/j.cyto.2012.12.003. Epub 2013 Jan 5.
Recently, a new subpopulation of T cells, the Th17 subset, has been implicated in autoimmune diseases. Its development is influenced by IL-27, expressed in macrophages or dendritic cells. IL-27 blockage delays the onset of diabetes in non obese diabetes mouse, but its role in type 1 diabetes (T1D) in human has not been reported yet. The aim of this study was identify variants in the entire coding regions of IL-27 gene, including the 5' proximal region, and their possible association with the disease.
Those regions were amplified by polymerase chain reaction followed by automatic sequencing and restriction fragments length polymorphisms. The cohort involved 614 individuals - 318 patients with T1D (19.6 ± 11.2 y, 129M/189F) and 296 healthy control subjects (30.3 ± 13.2 y, 131M/165F).
We identified eight allelic variants in the 5' proximal and coding regions of IL-27 gene, including two new variants: the c.-324 C>T in the 5' proximal region and the c.521 G>C in exon 5. None of these variants compromised transcription factor binding sites or the protein structure. The frequency of the alleles and genotypes of IL-27 variants did not differ between T1D patients and controls. There was no association between IL27 variants with gender, ethnicity, age at diagnosis of diabetes or presence of pancreatic and extrapancreatic autoantibodies.
Our findings suggest that allelic variants in IL27 are not associated with susceptibility to T1D in a Brazilian population.
最近,一种新的 T 细胞亚群——Th17 亚群,被认为与自身免疫性疾病有关。其发展受巨噬细胞或树突状细胞表达的 IL-27 影响。IL-27 阻断可延迟非肥胖型糖尿病小鼠糖尿病的发生,但尚未报道其在人类 1 型糖尿病(T1D)中的作用。本研究旨在鉴定 IL-27 基因整个编码区(包括 5'近端区)的变异及其与疾病的可能关联。
通过聚合酶链反应扩增这些区域,然后进行自动测序和限制片段长度多态性分析。该队列包括 614 名个体——318 名 T1D 患者(19.6±11.2 岁,129 名男性/189 名女性)和 296 名健康对照(30.3±13.2 岁,131 名男性/165 名女性)。
我们在 IL-27 基因的 5'近端和编码区鉴定出 8 种等位基因变异,包括 2 种新变异:5'近端的 c.-324 C>T 和外显子 5 的 c.521 G>C。这些变异均不影响转录因子结合位点或蛋白结构。IL-27 变异的等位基因和基因型频率在 T1D 患者和对照组之间无差异。IL27 变异与性别、种族、糖尿病诊断时的年龄或胰腺和胰外自身抗体的存在均无关联。
我们的研究结果表明,巴西人群中 IL27 的等位基因变异与 T1D 的易感性无关。