Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, LKS Faculty of Medicine,The University of Hong Kong, 21 Sassoon Road, Hong Kong, China.
Hum Mol Genet. 2011 Feb 1;20(3):601-7. doi: 10.1093/hmg/ddq474. Epub 2010 Nov 2.
Systemic lupus erythematosus (SLE) is an autoimmune disease with a strong genetic involvement. The susceptibility genes identified so far can only explain a small proportion of disease heritability. Through a genome-wide association in a Hong Kong Chinese cohort and subsequent replication in two other Asian populations, with a total of 3164 patients and 4482 matched controls, we identified association of ELF1 (E74-like factor 1) with SLE (rs7329174, OR = 1.26, joint P= 1.47 × 10(-8)). ELF1 belongs to the ETS family of transcription factors and is known to be involved in T cell development and function. Database analysis revealed transcripts making use of three alternative exon1s for this gene. Near equivalent expression levels of distinct transcripts initiated from alternative exon1s were detected in peripheral blood mononuclear cells from both SLE patients and healthy controls. Although a direct association of rs7329174 with the three forms of transcripts for this gene was not detected, these findings support an important role of ELF1 in SLE susceptibility and suggest a potentially tight regulation for the expression of this gene.
系统性红斑狼疮 (SLE) 是一种自身免疫性疾病，具有很强的遗传参与。到目前为止，已鉴定的易感基因只能解释疾病遗传率的一小部分。通过对香港华人队列进行全基因组关联研究，并在另外两个亚洲人群中进行后续复制，共纳入 3164 名患者和 4482 名匹配对照，我们发现 ELF1（E74 样因子 1）与 SLE 相关(rs7329174，OR=1.26，联合 P=1.47×10(-8))。ELF1 属于 ETS 转录因子家族，已知其参与 T 细胞发育和功能。数据库分析显示，该基因有三个不同的外显子 1 可以转录出不同的转录本。在 SLE 患者和健康对照者的外周血单核细胞中，均检测到从不同外显子 1 起始的不同转录本具有相当的表达水平。虽然未检测到 rs7329174 与该基因的三种转录本之间存在直接关联，但这些发现支持 ELF1 在 SLE 易感性中的重要作用，并提示该基因的表达可能受到严格调控。
