SCGB3A2基因启动子区单核苷酸多态性功能与Graves病易感性研究  

Functional single-nucleotide polymorphisms in the SCGB3A2 promoter are associated with susceptibility to Graves＇ disease

作　　者：梁军[1] 王玉[1] 赵双霞[2] 施静艺[2] 彭永德[3] 高冠起 潘春明[2] 袁国跃[5] 韩兵[2] 苏青[6] 高聆[7] 陈名道[2] 赵家军[7] 宋怀东[2] 

机构地区：[1]江苏省徐州市中心医院,徐州医学院,徐州临床学院内分泌科,221009 [2]上海交通大学附属瑞金医院医学分子中心、医学基因组学国家重点实验室、上海市内分泌代谢病研究所 [3]上海交通大学附属第一人民医院内分泌科 [4]山东省临沂人民医院内分泌科 [5]江苏大学附属医院内分泌科 [6]上海交通大学医学院附属新华医院内分泌科 [7]山东大学附属省立医院内分泌科

出　　处：《中华内分泌代谢杂志》2013年第2期102-107,共6页Chinese Journal of Endocrinology and Metabolism

基　　金：国家高科技项目（863）;国家自然科学基金（30530370、30971595、30470816、30771017）

摘　　要：目的 探讨SCGB3A2基因（secretoglobin family 3A member 2, SCGB3A2）启动子区单核苷酸多态性（single-nucleotide polymorphisms, SNPs）功能与Graves病（GD）易感性。方法 应用荧光素酶检测、实时定量逆转录-聚合酶链反应、等位基因特异性定量转录等方法，对SCGB3A2基因启动子区（SNPs in promoter,pSNPs；SNP76、SNP75以及SNP74）进行体内外功能分析。结果 SCGB3A2基因启动子-荧光素酶报告质粒pGL3-（SNP76＋SNP75）、pGL3-（SNP76＋SNP74）以及pGL3-（SNP76＋SNP75＋SNP74）的荧光素酶活性均减弱。T等位基因能够竞争结合AG等位基因，比非易感等位基因AG有更强的结合转录因子能力。携带有SNP76＋SNP75和SNP76＋SNP74者SCGB3A2基因的表达低于不携带该变异者。体内外功能分析显示，SNP76＋SNP75和SNP76＋SNP74单倍型可使SCGB3A2基因表达下调。结论 SCGB3A2基因pSNPs（SNP76、SNP75以及SNP74）的功能与GD易感性相关。Objective To investigate the association of functional single-nucleotide polymorphisms（SNPs） in the SCGB3A2 promoter with susceptibility to Graves′ disease（GD）. Methods Functional analysis was carried out in vivo and in vitro in the pSNPs （SNP76, SNP75, and SNP74） by means of luciferase assays, real-time reverse transcriptase-polymerase chain reaction, and allele-specific transcript quantification. Results The luciferase activities of pGL3-（SNP76＋SNP75）, pGL3-（SNP76＋SNP74）, and pGL3-（SNP76＋SNP75＋SNP74） were decreased. T allele was able to compete for binding AG allele and the susceptible allele and showed higher binding affinity with the transcription factor than the non-susceptible allele AG. The expression of the SCGB3A2 gene with SNP76＋SNP75 and SNP76＋SNP74 alleles was significantly lower than that in samples with wild-type alleles. Functional analysis in vivo and in vitro suggested that SCGB3A2 were lower in individuals with the haplotype of the SNP76 ＋SNP74 and SNP76＋SNP75. Conclusion A significant association of GD with the functional SNPs in the SCGB3A2 gene has been identified.

关 键 词：格雷夫斯病 SCGB3A2基因 多态性 单核苷酸 

分 类 号：R581.1[医药卫生—内分泌]