Rheumatology Section, Imperial College, London W12 0NN, UK.
Hum Mol Genet. 2011 Mar 1;20(5):1026-33. doi: 10.1093/hmg/ddq536. Epub 2010 Dec 13.
Systemic lupus erythematosus (SLE) is an autoimmune disease which behaves as a complex genetic trait. At least 20 SLE risk susceptibility loci have been mapped using both candidate gene and genome-wide association strategies. The gene encoding the pro-inflammatory cytokine, IL18, has been reported as a candidate gene showing an association with SLE. This pleiotropic cytokine is expressed in a range of immune cells and has been shown to induce interferon-γ and tumour necrosis factor-α. Serum interleukin-18 has been reported to be elevated in patients with SLE. Here we aimed to densely map single nucleotide polymorphisms (SNPs) across IL18 to investigate the association across this locus. We genotyped 36 across IL18 by Illumina bead express in 372 UK SLE trios. We also genotyped these SNPs in a further 508 non-trio UK cases and were able to accurately impute a dense marker set across IL18 in WTCCC2 controls with a total of 258 SNPs. To improve the study's power, we also imputed a total of 158 SNPs across the IL18 locus using data from an SLE genome-wide association study and performed association testing. In total, we analysed 1818 cases and 10 770 controls in this study. Our large well-powered study (98% to detect odds ratio = 1.5, with respect to rs360719) showed that no individual SNP or haplotype was associated with SLE in any of the cohorts studied. We conclude that we were unable to replicate the SLE association with rs360719 located upstream of IL18. No evidence for association with any other common variant at IL18 with SLE was found.
系统性红斑狼疮（SLE）是一种自身免疫性疾病，表现为复杂的遗传特征。 已经使用候选基因和全基因组关联策略在至少 20 个 SLE 风险易感基因座上进行了映射。 编码促炎细胞因子 IL18 的基因已被报道为与 SLE 相关的候选基因。 这种多效细胞因子在多种免疫细胞中表达，并已显示出诱导干扰素-γ和肿瘤坏死因子-α。 已经报道血清白细胞介素-18 在 SLE 患者中升高。 在这里，我们旨在通过全基因组关联研究对 IL18 进行单核苷酸多态性（SNP）的密集作图，以研究该基因座的关联。 我们通过 Illumina bead express 在 372 个英国 SLE 三核苷酸中对 IL18 进行了 36 个 SNP 的基因分型。 我们还在另外 508 个非三核苷酸英国病例中对这些 SNP 进行了基因分型，并能够在 WTCCC2 对照中准确地在 IL18 上对密集标记集进行遗传分型，总共 258 个 SNP。 为了提高研究的功效，我们还使用 SLE 全基因组关联研究的数据对 IL18 上的总共 158 个 SNP 进行了遗传分型，并进行了关联测试。 在这项研究中，我们总共分析了 1818 例病例和 10770 例对照。 我们的大型、功能强大的研究（98％以检测到比值比= 1.5，相对于 rs360719）表明，在所研究的任何队列中，都没有单个 SNP 或单体型与 SLE 相关。 我们得出结论，我们无法复制位于 IL18 上游的 rs360719 与 SLE 的关联。 没有发现与 IL18 上的任何其他常见变异与 SLE 相关的证据。
