中文摘要：

目的对中国人群系统性红斑狼疮（SLE）易感基因前B淋巴细胞白血病转录因子（PBXl）3’端非翻译区的结构变异进行分析及功能研究。方法利用焦磷酸测序技术（Ryrosequencing）对273名正常人，633例狼疮患者标本进行rs3185695基因分型，进行病例对照研究。通过实时定量聚合酶链反应（PCR）、Pyrosequencing以及报告基因活性测定等方法进行等位基因特异性基因表达研究，分析PBXl基因3’端非翻译区的rs3185695对基因表达的影响。结果中国人群中rs3185695次要等位基因A在SLE患者组和正常对照组的频率分别为11．4％和4．2％，差异具有统计学意义（P〈0．01），次要等位基因A与SLE发病相关。rs3185695为A／G杂合子的cDNA样本中PBXl基因的mRNA水平表达量明显低于G／G纯合子，带有A等位基因的转录本水平明显低于G等位基因。rs3185695A等位基因的重组质粒报告基因的活性明显低于G等位基因。结论中国人群中PBXl基因3’端非翻译区的rs3185695A与SLE发病关联，该单核苷酸多态性（SNP）位点G→A的变异能下调PBXl基因的表达，继而调节其调控通路下游基因的转录水平，参与疾病的发生。

英文摘要：

Objective To study the structural variation and the function of the 3＇ untranslated Region of PBX1 gene, a susceptibile gene for systemic lupus erythematosus （SEE）, in the pathogenesis of SLE in Chinese. Methods Case-control association analysis was conducted in 273 controls and 633 SLE patients for rs3185695 by Pyrosequencing. The function of rs3185695 was analyzed by real-time PCR, Pyrosequencing and reporter gene activity determination. Results Frequencies of the minor allele A of rs3185695 in SLE and controls were 11.4% and 4.2% respectively （P〈0.01）, and the minor allele A showed association with SLE. The mRNA expression of PBXI gene in A/G heterozygous samples was significantly lower than that in G/G homozygous samples, and the expression of transcript containing A allele was significantly lower than G allele. The reporter gene activities of A allele of rs3185695 were markedly lower than G allele. Conclusion In Chinese, the rs3185695A in the 3＇ Untranslated Region of PBX1 is associated with SLE, and the variation of this SNP （G→A） may down-regulate the expression of PBX1 gene, which then mediates the transcript expression of downstream genes in the pathway and eventually being involved in the pathogenesis of SLE.