泛素羧基末端水解酶L1基因S18Y多态性与散发性阿尔茨海默病的相关性分析

目的探讨泛素羧基末端水解酶L1(UCH-L1)基因的S18Y多态性在散发性阿尔茨海默病(AD)发病机制中的作用。方法利用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测116例散发性AD患者和123例正常人UCH-L1基因S18Y多态性分布后,进行病例-对照相关分析。结果S18Y多态性等位基因及基因型频率在AD组和正常对照组差别无统计学差异;按发病年龄对AD组进行分层后,亦未显示S18Y多态性与散发性AD相关;按性别分层后,女性AD组Y等位基因和YY基因型频率明显低于女性正常对照组(分别为P=0.003和P=0.015)。结论Y等位基因和YY基因型在女性对散发性AD的发病可能有一定的保护作用,机制可能与多态性引起的UCH-L1功能改变及不同的危险因素相互作用有关。

Genetic association of the Ubiquitin Carboxy-terminal Hydrolase -L1 gene S18Y polymorphism with sporadic Alzhermer's disease

Objectives: To explore the role of S18Y polymorphism of Ubiquitin Carboxy-terminal Hydrolase-L1 (UCH-L1) gene in the pathogenesis of sporadic Alzhermer's disease (AD). Methods: The UCH-L1 S18Y polymorphism in 116 sporadic AD patients and 123 healthy controls were detected by PCR-restriction fragment length polymorphism (RFLP) analysis and data were analyzed with a case-control study. Results: The allele and genotype data as well as data after stratification by age of onset failed to demonstrate any association between AD and S18Y polymorphism. However, after stratification by sex, female AD patients showed significantly less frequencies of Y allele and YY genotype in S18Y than female controls (P=0.003 and P=0.015 respectively). Conclusion: Y allele and YY genotype of S18Y polymorphism in the UCH-L1 gene may have a protective effect against sporadic AD in female subjects due to altering the function of UCH-L1 and the interactions among different risk factors.