Sex-specific association of X-linked Toll-like receptor 7 (TLR7) with male systemic lupus erythematosus
Sex-specific association of X-linked Toll-like receptor 7 (TLR7) with male systemic lupus erythematosus
复制标题
X连锁Toll样受体7（TLR7）与男性系统性红斑狼疮的性别特异性关联
DOI：
10.1073/pnas.1001337107
复制
发表时间：
2010-09-07
影响因子：
11.1
通讯作者：
Tsao, Betty P.
中科院分区：
文献类型：
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作者：
Shen, Nan;Fu, Qiong;Tsao, Betty P.
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。先前发现，Toll样受体7（Tlr7）重复可促进雄性BXSB小鼠出现狼疮样疾病，这促使我们对人类SLE中的TLR7进行评估。通过候选基因方法，我们在9274名东亚人中发现并重复验证了TLR7的3'非翻译区单核苷酸多态性rs3853839（G/C）与SLE的关联（合并P值 = 6.5×10⁻¹⁰），且在男性受试者中的作用强于女性[比值比，男性与女性 = 2.33（95%置信区间 = 1.64 - 3.30）与1.24（95%置信区间 = 1.14 - 1.34）；P = 4.1×10⁻⁴]。G等位基因携带者的TLR7转录本增加，且干扰素特征比C等位基因携带者更显著；杂合子的G等位基因转录本比C等位基因高2.7倍。这些数据确定了I型干扰素通路基因TLR7中的一种功能性多态性，它使个体易患SLE，尤其是在中国和日本男性受试者中。
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 (Pcombined = 6.5 × 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 × 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.