title: Protective effect of interleukin-23A (IL23A) haplotype variants on type 1A diabetes mellitus in a Brazilian population.
abstract: The Interleukin 23 (IL-23) has a central role in autoimmunity. Allelic variants of p19 subunit of IL-23 (IL23A) and IL-23 receptor (IL23R) genes and increased IL-23 serum concentrations were associated with autoimmune diseases. We therefore searched for variants of IL23A and IL23R that could predispose to Type 1 diabetes (T1D). The coding regions and boundary intron sequences of IL23A were sequenced. Variants of IL23A and of IL23R were also genotyped. Pancreatic and extrapancreatic autoantibodies and IL-23 serum levels were determined. The cohort involved 370 patients with T1D and 351 healthy control subjects. We observed only one coding IL23A variant (rs11171806 G>A) out of the 6 described in databases. As the G alleles of rs11171806 and rs2066808 variants of IL23A gene were in strong linkage disequilibrium (D'=-0.825 for controls, p<2.0 × 10(-6) and D'=-0.902, p<2.0 × 10(-17) for patients), further analyses were performed with the haplotypes. The GG haplotype was more frequent in controls (16.7%) than in T1D patients (9.5%), conferring a protection to T1D (OR=0.53; pc=0.0003). No association was found between IL23A allelic variants with age at diagnosis of diabetes, C-peptide levels or frequency of autoantibodies. IL23R variants (rs10889677 and rs11209026) frequency and IL-23 serum concentrations were similar between groups. The GG haplotype of lL23A variants (rs11171806 and rs2066808) was protective against T1D. IL23R variants (rs11209026 and rs10889677) were not associated with T1D. IL-23 serum concentrations did not differ between groups.
authors.affiliation: Laboratório de Carboidratos e Radioimunoensaio (LIM18), Faculdade de Medicina da Universidade de São Paulo, Departamento de Endocrinologia, Brazil. vinicius.scosta@usp.br
authors.forename: V S
authors.initials: VS
authors.lastname: Costa
authors.forename: A S
authors.initials: AS
authors.lastname: Santos
authors.forename: R T
authors.initials: RT
authors.lastname: Fukui
authors.forename: T C C
authors.initials: TC
authors.lastname: Mattana
authors.forename: S R
authors.initials: SR
authors.lastname: Matioli
authors.forename: M E R
authors.initials: ME
authors.lastname: Silva
mesh_terms: D000328:Adult; D000483:Alleles; D001323:Autoantibodies / Q000097:blood; D001483:Base Sequence; D001938:Brazil; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D053760:Interleukin-23 Subunit p19 / Q000097:blood* / Q000235:genetics* / Q000378:metabolism; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D018123:Receptors, Interleukin / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D001323:Autoantibodies; C508840:IL23A protein, human; C515500:IL23R protein, human; D053760:Interleukin-23 Subunit p19; D018123:Receptors, Interleukin