Alzheimer病患者线粒体DNA点突变的研究

目的旨在观察Alzheimer病(Alzheimerdisease,AD)患者线粒体DNA(mitochondrialDNA,mtDNA)上点突变的情况,并探讨mtDNA点突变与AD发生的关联性。方法入组了111例AD患者作为AD组和性别/年龄与之相匹配的正常老人117名组成对照组,应用PCR-RFLP的方法对被研究对象mtDNA上分别位于第4336、5460和8021三个位置的点突变情况进行检测。结果第4336位置上的碱基未发现存在突变的现象。第8021位置上的碱基仅在正常老人组内检测到1例突变型,其余均为野生型。在第5460位置上对照组突变率为2.6%(3/117),AD老人组中突变率为6.3%(7/111),显著性检验χ2=1.902,P=0.168。结论在我国上海汉族人群中线粒体DNA上第4336位置上可能不存在点突变的现象,第8021位置上突变也很少发生,在第5460位置上的碱基可能出现A或T的点突变,但这种突变的发生可能与AD的发生无直接关联。

A study on point mutations of mitochondrial DNA in the patients with Alzheimer's disease

Objective: To investigate the mutations of mitochondrial DNA(mtDNA) in the patients with Alzheimer's disease(AD) and to detect the association between the mutations and AD.Methods: 111 patients with AD and 117 age-matched healthy comtrols were involved.The mutations at the positions of 4336,5460 and 8021 in mtDNA were detected with PCR-RFLP.Results:The 4336G mutation was not present in our AD patients and the age-matched healthy samples.The 8021 A/G mutation was not present in any of our 111 AD samples but occurred in 1 individual of 117 (0.85%) controls.The 5460A or T mutation occurred in 7 of 111 (6.3%) AD patients and in 117 age-matched contols,3 individuals (2.6%) bore the mutation.By statistical analysis,the difference between the two groups was not significant (chisq=1.902,P=0.168).Conclusion:In Chinese Han Populations,the 4336G mutation maybe does not exist,the 8021 A/G mutation seldom occurs, and at 5460 position,there is A or T mutation,but the mutation maybe does not associated with AD.