title: Two SNPs in NLRP3 gene are involved in the predisposition to type-1 diabetes and celiac disease in a pediatric population from northeast Brazil.
abstract: Recent findings provide evidence of the critical role of innate immunity NALP1/NLRP1 and NALP3/NLRP3/CIAS1 genes in inflammatory diseases, and also in the predisposition to autoimmune disorders. We evaluated the possible association of five single nucleotide polymorphisms (SNPs), two in NLRP1 gene and three in NLRP3 gene, in pediatric patients from the north eastern region of Brazil affected by type-1 diabetes (T1D, n = 196), celiac disease (CD, n = 59), and atopic dermatitis (AD, n = 165), and in healthy individuals (n = 192). Our results demonstrated that NLRP3 rs10754558 SNP was associated specifically to T1D (p = 4exp-3) and NLRP3 rs358294199 SNP to CD (p = 5exp-4) in the Brazilian population. Despite its strong association with T1D in Norwegian population, NLRP1 was not associated with T1D, in the Brazilian population. According to previous studies in Caucasoid cohorts, NLRP1 and NLRP3 seemed not to be associated to AD. Since it has been reported that IL-1 beta has a systemic effect in the lost of the immunologic tolerance and that NALP3 inflammasome is directly involved in the production of this pro-inflammatory cytokine, we hypothesized that variations in NLRP3 could belong to a predisposing genetic background that contribute to the development of autoimmune diseases.
authors.affiliation: Medical Genetic Service, Institute for Maternal and Child Health - IRCCS Burlo Garofolo, Trieste, Italy. pontillo@burlo.trieste.it
authors.forename: A
authors.initials: A
authors.lastname: Pontillo
authors.forename: L
authors.initials: L
authors.lastname: Brandao
authors.forename: R
authors.initials: R
authors.lastname: Guimaraes
authors.forename: L
authors.initials: L
authors.lastname: Segat
authors.forename: J
authors.initials: J
authors.lastname: Araujo
authors.forename: S
authors.initials: S
authors.lastname: Crovella
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000293:Adolescent; D001938:Brazil; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D002446:Celiac Disease / Q000235:genetics / Q000276:immunology*; D002648:Child; D004247:DNA / Q000737:chemistry / Q000235:genetics; D003876:Dermatitis, Atopic / Q000235:genetics / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology*; D008297:Male; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics / Q000276:immunology*
chemical_list: D020413:3' Untranslated Regions; D002352:Carrier Proteins; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D004247:DNA