Department of Pediatrics, Yokohama City University School of Medicine, Kanazawa-ku, Yokohama, Kanagawa, Japan.
PLoS One. 2013 Aug 30;8(8):e72551. doi: 10.1371/journal.pone.0072551. eCollection 2013.
Systemic lupus erythematosus (SLE) is a systemic multisystem autoimmune disorder influenced by genetic background and environmental factors. Our aim here was to replicate findings of associations between 7 of the implicated single nucleotide polymorphisms (SNPs) in IRF5, BLK, STAT4, TNFAIP3, SPP1, TNIP1 and ETS1 genes with susceptibility to childhood-onset SLE in the Japanese population. In particular, we focused on gender differences in allelic frequencies.
METHODOLOGY/PRINCIPAL FINDINGS: The 7 SNPs were genotyped using TaqMan assays in 75 patients with childhood-onset SLE and in 190 healthy controls. The relationship between the cumulative number of risk alleles and SLE manifestations was explored in childhood-onset SLE. Logistic regression was used to test the effect of each polymorphism on susceptibility to SLE, and Wilcoxon rank sum testing was used for comparison of total risk alleles. Data on rs7574865 in the STAT4 gene and rs9138 in SPP1 were replicated for associations with SLE when comparing cases and controls (corrected P values ranging from 0.0043 to 0.027). The rs2230926 allele of TNFAIP3 was associated with susceptibility to SLE in males, but after Bonferroni correction there were no significant associations with any of the other four SNPs in IRF5, BLK, TNIP1 and ETS1 genes. The cumulative number of risk alleles was significantly increased in childhood-onset SLE relative to healthy controls (P = 0.0000041). Male SLE patients had a slightly but significantly higher frequency of the TNFAIP3 (rs2230926G) risk allele than female patients (odds ratio [OR] = 4.05, 95% confidence interval [95%CI] = 1.46-11.2 P<0.05).
Associations of polymorphisms in STAT4 and SPP1 with childhood-onset SLE were confirmed in a Japanese population. Although these are preliminary results for a limited number of cases, TNFAIP3 rs2230926G may be an important predictor of disease onset in males. We also replicated findings that the cumulative number of risk alleles was significantly increased in childhood-onset SLE.
系统性红斑狼疮（SLE）是一种全身性多系统自身免疫性疾病，受遗传背景和环境因素的影响。我们的目的是在日本人群中复制与 IRF5、BLK、STAT4、TNFAIP3、SPP1、TNIP1 和 ETS1 基因中 7 个受累单核苷酸多态性（SNP）与儿童发病的 SLE 易感性相关的发现。特别是，我们关注了等位基因频率的性别差异。
方法/主要发现：使用 TaqMan 测定法对 75 例儿童发病的 SLE 患者和 190 名健康对照者的 7 个 SNP 进行基因分型。在儿童发病的 SLE 中，探讨了累积风险等位基因数与 SLE 表现之间的关系。使用逻辑回归检验每个多态性对 SLE 易感性的影响，并用 Wilcoxon 秩和检验比较总风险等位基因。在比较病例和对照时，STAT4 基因中的 rs7574865 和 SPP1 中的 rs9138 的数据得到了 rs2230926 等位基因与 SLE 相关的复制（校正 P 值范围从 0.0043 到 0.027）。TNFAIP3 的 rs2230926 等位基因与男性 SLE 的易感性相关，但经 Bonferroni 校正后，IRF5、BLK、TNIP1 和 ETS1 基因中的其他四个 SNP 均无显著相关性。与健康对照组相比，儿童发病的 SLE 中累积风险等位基因数显著增加（P=0.0000041）。男性 SLE 患者的 TNFAIP3（rs2230926G）风险等位基因频率略高于女性患者（比值比[OR] = 4.05，95%置信区间[95%CI] = 1.46-11.2，P<0.05）。
STAT4 和 SPP1 多态性与日本人群中儿童发病的 SLE 相关的关联得到了证实。尽管这是针对有限数量病例的初步结果，但 TNFAIP3 rs2230926G 可能是男性发病的重要预测因子。我们还复制了累积风险等位基因数在儿童发病的 SLE 中显著增加的发现。
