中国人Wilson病ATP7B基因启动子区的研究

Study on promoter region of ATP7B gene in Chinese with Wilson disease

目的研究中国人Wilson病(WD)ATP7B基因启动子区的序列和结构,发现存在的多态和突变情况。方法检测60例无亲缘关系的WD患者和20例正常人的基因组DNA序列并进行分析。结果(1)在正常对照和WD患者的启动子区-190位和-78位(转录起始点为+1)均发现存在单个碱基的不同;(2)60例WD患者中,3例发现存在-504位G→C的突变,其中2例为纯合突变,1例为杂合突变,在正常对照中未发现此改变。(3)60例WD患者中,2例发现存在-782位A→G的突变,其中1例为纯合突变,另1例为杂合突变,在正常对照中未发现此改变。结论WD基因的转录直接受铜或其他重金属的调节。中国人WD基因启动子区序列存在的2个多态位点均位于已知的转录调控元件结构之外,提示核苷酸多态对启动子调控基因的表达不会产生影响。启动子区的突变也是WD的分子发病机制之一。提示WD基因的分子发病机制是多样又复杂。

Objective To evaluate polymorphisms and mutations in the promoter region of ATP7B gene of Chinese by analyzing the sequence. Methods Sequence of DNA from peripheral blood obtained from 60 WD patients and 20 normal people was study. Results （ 1 ） There was single mutation in two polymorphisms at positions - 190, - 78 of the promoter region. It is same in normal control and WD patients;（2）Three of 60 WD patients presented G→C base substitution mutation at the positiion -504. Two were homozygous mutation, the other was heterozygous mutation. （3）Two of 60 WD patients presented A→G base substitution mutation at the position -782, one was homozygous mutation, the other was heterozygous mutation. Normal control group didn＇t show this kind of mutation. Conclusion Transeription of WD gene is directly regulated by copper and other metal ions. There are two polymorphisms in the promoter region of WD gene outside of the transcription regulatory elements. It show that two polymorphisms play no role in the expression of the WD gene. It suggests that the mutation of the promoter region is one reason of the pathogenesis and make us recognize that the mechanisms on WD pathogenesis are diverse and complex.