Key result
The IL18 rs360719 C-allele was significantly associated with increased susceptibility to systemic lupus erythematosus (Pooled OR 1.37; 95% CI 1.21-1.54; P=3.8E-07).
Why the study?
Is the IL18 rs360719 variant associated with susceptibility to systemic lupus erythematosus?
Case-Control
Yes
Is the IL18 rs360719 variant associated with susceptibility to systemic lupus erythematosus?
Odds Ratio: 1.37 (95% CI 1.21–1.54)
p-value: p=3.8E-07
The novel IL18 rs360719 variant is associated with increased susceptibility to systemic lupus erythematosus and increased IL18 gene expression.
IL18 variant association with SLE is hypothesis-generating; leaves open replication, functional validation, and therapeutic relevance.
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.
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Sánchez et al. (2009) conducted a case-control in Systemic lupus erythematosus. IL18 rs360719 C-allele vs. Non-carriers was evaluated on Susceptibility to systemic lupus erythematosus (OR 1.37, 95% CI 1.21-1.54, p=3.8E-07). The IL18 rs360719 C-allele was significantly associated with increased susceptibility to systemic lupus erythematosus (Pooled OR 1.37; 95% CI 1.21-1.54; P=3.8E-07).
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