Shenzhen Key Laboratory for Translational Medicine of Dermatology, Shenzhen-PKU-HKUST Medical Center, Department of Dermatology, Shenzhen Hospital Peking University, Biomedical Research Institute, Shenzhen-PKU-HKUST Medical Center, Shenzhen, Guangdong.
Rheumatology (Oxford). 2011 Jul;50(7):1201-5. doi: 10.1093/rheumatology/keq439. Epub 2011 Jan 27.
Th1 cells have been implicated as the causal agents in the pathogenesis of autoimmunity. SLE represents the classical prototype of systemic autoimmune disease. Copy number variations (CNVs) have been discovered to have phenotypic consequences and associate with various types of diseases. The current study aims to explore a possible association between CNVs of Th1 cell-related genes and the risk of SLE.
Genomic DNA and RNA from 532 SLE patients and 576 healthy controls were extracted. CNVs of Th1 cell-related genes (T-bet, Stat4, IL-12A, IL-12B, IFN-γ, IP-10 and CXCR3) as well as Th2 and Treg cell-related genes (c-Mef, GATA3, Foxp3, IL-6 and TGF-β) were examined, and mRNA levels of IL-12B and T-bet were examined.
Frequencies of IL-12B and T-bet CNVs in SLE patients were significantly higher than those in healthy controls. CNVs of IL-12B and T-bet had no synergistic contribution to SLE. The mRNA levels of IL-12B and T-bet in the samples with more than two copies of DNA were significantly higher than those with two copies of DNA.
CNVs of IL-12B and T-bet are associated with the risk of SLE.
Th1 细胞被认为是自身免疫发病机制中的致病因素。SLE 代表系统性自身免疫疾病的经典原型。已发现拷贝数变异 (CNV) 具有表型后果，并与各种类型的疾病相关。本研究旨在探讨 Th1 细胞相关基因的 CNV 与 SLE 风险之间的可能关联。
从 532 例 SLE 患者和 576 例健康对照中提取基因组 DNA 和 RNA。检测了 Th1 细胞相关基因（T-bet、Stat4、IL-12A、IL-12B、IFN-γ、IP-10 和 CXCR3）以及 Th2 和 Treg 细胞相关基因（c-Mef、GATA3、Foxp3、IL-6 和 TGF-β）的 CNV，同时检测了 IL-12B 和 T-bet 的 mRNA 水平。
SLE 患者中 IL-12B 和 T-bet 的 CNV 频率明显高于健康对照组。IL-12B 和 T-bet 的 CNV 对 SLE 没有协同作用。DNA 拷贝数超过两份的样本中 IL-12B 和 T-bet 的 mRNA 水平明显高于两份 DNA 的样本。
IL-12B 和 T-bet 的 CNV 与 SLE 的风险相关。
