【摘要】 目的了解中国人肝豆状核变性(WD)ATP7B基因5′UTR及启动因子区域分子特征,探讨不同人种该区域基因多态与突变的分布。方法采用聚合酶链反应-单链构象特异性(PCR-SSCP)和DNA序列分析技术,对110例WD患者和90例健康对照儿童进行ATP7B基因5′UTR及启动因子区域分子特征研究。结果1.共发现5种基因改变:-1294T→G、-105C→G、-116C→T、-132delGCCGC和-75A→C,前三者未见报道,-132delGCCGC未见国内报道。2.-132delGCCGC和-75A→C位点等位基因均占70%以上,发生频率较高,且98%的患者呈完全连锁状态,二者相关性为96.9%。3.国内外ATP7B基因启动子和5′UTR区域至今仅发现约20种多态,包括本课题发现的5种类型。中国人ATP7B基因启动子的多态主要分布于EXON1侧翼序列,其多态的分布和种族密切相关。结论发现ATP7B基因多态5种,其中-1294T→G、-105C→G、-116C→T为首次报道;-132delGCCGC和-75A→C几乎呈连锁存在。中国人WD患者的ATP7B基因启动子和5′UTR结构改变大部分分布在EXON1侧翼序列。中国人启动子部分不存在突变热点。更多还原

【Abstract】 Objective To detect molecular characterization of the promoter and 5′UTR region of ATP7B gene in Chinese children with Wilson disease (WD) and explore the distribution of polymorphisms and mutations in different ethnicity.Methods One hundred and ten patients with WD and 90 healthy children were enrolled into the study and analyzed by polymerase chain reaction-single strand configuration polymorphism (PCR-SSCP) and DNA sequence analysis.Results 1.Five polymorphisms were identified as follows, -1294T→G,-105C→G,-116C→T ,-132delGCCGC and -75A→C(transcription start site as +1). The former three ones had never been reported before. The fourth one had not been reported either in China. 2.The polymorphism -132delGCCGC and -75A→C both exhibited with allelic frequency at above 70%, which was much higher than other races. The -132delGCCGC polymorphism shared almost complete linkage disequilibrium with the -75A→C polymorphism (in 98% patients) and their regularity was 96.9%.3. Almost all the polymorphisms distributed in flanking sequence of EXON 1 in Chinese. Race and geological distribution may be dominant factors of the variability of promoter and 5′UTR region of ATP7B gene.Conclusions Three novel polymorphisms and a linkage disequilibrium with the -132delGCCGC and -75A→C were identified in Chinese with WD. It also suggests that the mutation in the promoter of ATP7B is uncommon in Chinese patients.更多还原