狼疮易感基因PBXl 3＇端非翻译区的结构变异及其功能分析  

Structural variation and function analysis of the 3＇ untranslated region of lupus susceptible gene PBX1

作　　者：钱晓霞[1] 唐元家[2] 黄新芳[1] 陈静[1] 倪旭鸣[2] 钱捷[1] 罗晓兵[2] 崔慧娟[1] 陈顺乐[1] 沈南[1] 

机构地区：[1]上海交通大学医学院附属仁济医院风湿病学科上海市风湿病学研究所,上海200001 [2]中国科学院上海生命科学研究院健康科学研究所,上海

出　　处：《中华风湿病学杂志》2007年第10期583-586,共4页Chinese Journal of Rheumatology

基　　金：基金项目：国家自然科学基金资助项目（3000154,30471613,30271224）;国家高科技研究发展计划（863计划）基金资助项目（2002AA229101）;上海市科学技术委员会登山计划重点项目（06JC14050）;上海市自然科学基金资助项目（05ZR14136）

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。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.

关 键 词：红斑狼疮 系统性 单核苷酸多态性 PBX1 功能 

分 类 号：R686[医药卫生—骨科学]