Shanghai Renji Hospital, Shanghai JiaoTong University School of Medicine, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, China.
Proc Natl Acad Sci U S A. 2010 Sep 7;107(36):15838-43. doi: 10.1073/pnas.1001337107. Epub 2010 Aug 23.
Systemic lupus erythematosus (SLE) is a multisystem, autoimmune disease that predominantly affects women. Previous findings that duplicated Toll-like receptor 7 (Tlr7) promotes lupus-like disease in male BXSB mice prompted us to evaluate TLR7 in human SLE. By using a candidate gene approach, we identified and replicated association of a TLR7 3'UTR SNP, rs3853839 (G/C), with SLE in 9,274 Eastern Asians (P(combined) = 6.5 x 10(-10)), with a stronger effect in male than female subjects [odds ratio, male vs. female = 2.33 (95% CI = 1.64-3.30) vs. 1.24 (95% CI = 1.14-1.34); P = 4.1 x 10(-4)]. G-allele carriers had increased TLR7 transcripts and more pronounced IFN signature than C-allele carriers; heterozygotes had 2.7-fold higher transcripts of G-allele than C-allele. These data established a functional polymorphism in type I IFN pathway gene TLR7 predisposing to SLE, especially in Chinese and Japanese male subjects.
系统性红斑狼疮 (SLE) 是一种多系统自身免疫性疾病，主要影响女性。先前的研究发现，重复 Toll 样受体 7 (Tlr7) 可促进雄性 BXSB 小鼠发生狼疮样疾病，这促使我们评估 TLR7 在人类 SLE 中的作用。通过候选基因方法，我们鉴定并复制了 TLR7 3'UTR SNP(rs3853839，G/C) 与东亚 9274 例患者 SLE 的关联（合并 P 值=6.5×10(-10)），该 SNP 在男性患者中的作用强于女性患者[比值比，男性比女性=2.33(95%CI=1.64-3.30)比 1.24(95%CI=1.14-1.34)；P=4.1×10(-4)]。G 等位基因携带者的 TLR7 转录本增加，IFN 特征更为明显，而 C 等位基因携带者则相反；杂合子的 G 等位基因转录本比 C 等位基因高 2.7 倍。这些数据确立了一种 I 型 IFN 通路基因 TLR7 的功能性多态性，可导致 SLE，尤其是中国和日本男性患者的 SLE。
