title: Identification of a new putative functional IL18 gene variant through an association study in systemic lupus erythematosus.
abstract: Interleukin-18 (IL-18) is a proinflammatory cytokine that plays an important role in chronic inflammation and autoimmune disorders. In this study, we aimed to determine the potential role of the IL18 gene in SLE. To define the genetic association of the IL18 and SLE, we have genotyped nine SNPs in an independent set of Spanish cases and controls. The IL18 polymorphisms were genotyped by PCR, using a predeveloped TaqMan allele discrimination assay. Two SNPs were still significant after fine mapping of the IL18 gene. The SNP (rs360719) surviving correction for multiple tests was genotyped in two replication cohorts from Italy and Argentina. After the analysis, a significance with rs360719 C-allele remained across the sets and after the meta-analysis (Pooled OR = 1.37, 95% CI 1.21-1.54, combined P = 3.8E-07, Pc = 1.16E-06). Quantitative real-time PCR was performed to assess IL18 mRNA expression in PBMC from subjects with different IL18 rs360719 genotypes. We tested the effect of the IL18 rs360719 polymorphism on the transcription of IL18 by electrophoretic mobility shift assay and western blot. We found a significant increase in the relative expression of IL18 mRNA in individuals carrying the rs360719 C-risk allele; in addition we show that the polymorphism creates a binding site for the transcriptional factor OCT-1. These findings suggest that the novel IL18 rs360719 variant may play an important role in determining the susceptibility to SLE and it could be a key factor in the expression of the IL18 gene.
authors: Instituto de Parasitología y Biomedicina López-Neyra, CSIC, Granada 18100, Spain. elena@ipb.csic.es
authors: Elena
authors: E
authors: Sánchez
authors: Rogelio J
authors: RJ
authors: Palomino-Morales
authors: Norberto
authors: N
authors: Ortego-Centeno
authors: Juan
authors: J
authors: Jiménez-Alonso
authors: Miguel A
authors: MA
authors: González-Gay
authors: Miguel A
authors: MA
authors: López-Nevot
authors: Julio
authors: J
authors: Sánchez-Román
authors: Enrique
authors: E
authors: de Ramón
authors: M Francisca
authors: MF
authors: González-Escribano
authors: Bernardo A
authors: BA
authors: Pons-Estel
authors: Sandra
authors: S
authors: D'Alfonso
authors: Gian Domenico
authors: GD
authors: Sebastiani
authors: Marta E
authors: ME
authors: Alarcón-Riquelme
authors: Javier
authors: J
authors: Martín
mesh_terms: D016022:Case-Control Studies; D002460:Cell Line; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics
chemical_list: D020382:Interleukin-18