Lack of association between IL27 gene variants and type 1 diabetes susceptibility

• Published in: Cytokine (Philadelphia, Pa.) Vol. 61; no. 2; pp. 349 - 352
• Main Authors: Santos, Aritania S., Melo, Maria E., Crisóstomo, Lindiane G., Fukui, Rosa T., Matioli, Sérgio R., Silva, Maria Elizabeth R.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-02-2013
• Subjects: Adult; Alleles; Animals; autoantibodies; autoimmune diseases; binding sites; Case-Control Studies; cytokines; dendritic cells; Diabetes Mellitus, Type 1 - genetics; exons; Female; gender; gene frequency; Gene Frequency - genetics; genes; Genetic Association Studies; Genetic Predisposition to Disease; genotype; Humans; IL-27 gene; insulin-dependent diabetes mellitus; Interleukins - genetics; macrophages; Male; Mice; nationalities and ethnic groups; Pancreatic and extra-pancreatic autoantibodies; patients; polymerase chain reaction; Polymorphism, Single Nucleotide - genetics; protein structure; T-lymphocytes; transcription factors; Type 1 diabetes; Young Adult; Type 1 diabetes; Pancreatic and extra-pancreatic autoantibodies; IL-27 gene
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2012.12.003

► The contribution of IL27 to human type 1 diabetes susceptibility was evaluated. ► IL27 was genotyped in 318 T1D patients and 296 healthy controls. ► Eight allelic variants, including two new ones, were identified. ► IL27 allelic variants did not predispose to type 1 diabetes in a Brazilian cohort. ► The frequency of estimated haplotypes was also similar between groups.
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±11.2y, 129M/189F) and 296 healthy control subjects (30.3±13.2y, 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.