摘要
目的探讨 PSEN2 基因启动子多态性与散发性阿尔茨海默病(Alzheimer disease,AD)的关联关系。方法采用聚合酶链反应-限制性片段长度多态性方法(PCR-RFLP)检测160例 AD 和160名年龄、性别相匹配的健康对照组的 PSEN2和 ApoE 基因型分布,并应用非条件 Logistic 回归分析判断 PSEN2和 ApoE 基因型是否为 AD 的危险因素。结果 PSEN2启动子+A/-A多态性频率在AD 组(+A/+A 58.8%,+A/-A 35.0%,-A/-A 6.3%)和对照组(+A/+A 65.0%,+A/-A33.1%,-A/-A 1.9%)间的差异无统计学意义(P=0.11)。年龄分层后,早发性和晚发性 AD 与相应对照组基因型频率差异仍无统计学意义(早发性 P=0.381,晚发性 P=0.287)。但根据 ApoE ε4携带与否分层后,在ε4非携带组 AD(+A/+A 50.7%,+A/-A 41.1%,-A/-A 8.2%)与对照组(+A/+A 65.0%,+A/-A 32.8%,-A/-A 2.2%)3种 PSEN2启动子基因型频率差异有统计学意义(P=0.038);在ε4携带组 AD 与对照组间 PSEN2基因型频率差异无统计学意义(P=0.549)。Logistic 回归表明,ApoE 基因型与 AD 的发生有关联关系(OR 5.2,95% CI 3.2～8.5,P<0.01),PSEN2基因型与 AD 的发生无关联关系(OR 1.4,95% CI 0.9～2.1,P=0.10),但在 ApoE ε4非携带组,PSEN2基因型与 AD 的发生有弱相关(OR 1.8,95% CI 1.1～3.0,P=0.02),ApoE 与 PSEN2之间无交互作用。结论 PSEN2启动子+A/-A 多态性可能是散发性 AD 比较弱的遗传危险因素,主要是在未携带 ApoE ε4等位基因的 AD 患者中具有一定的危险度。
Objective Alzheimer＇s disease （AD） is the most common neurodegenerative disorder of aging. Identifying novel AD genetic risk factors is important for understanding its pathogenesis. Presenilin- 2 （PSEN2） is one of the causative genes for familial AD. Polymorphism of the promoter region of PSEN2 has recently been reported to be associated with sporadic AD in a Russian population. The purpose of this study was to determine whether AD is associated with the PSEN2 gene polymorphism in a case-control study. Methods We examined PSEN2 and ApoE genotypes of 160 patients with AD and an equal number of age- and sex-matched controls from the same community by using PCR-RFLP method. Statistical analyses included a Chi-square test for homogeneity and a Logistic regression analysis. Results Examination of PSEN2 genotypes revealed no statistically significant differences in the frequency of the ＋ A/- A polymorphism when compared with the total sample of AD patients and control individuals （ P = 0. 11 ）. However, subgroup of ApoE ε4 non-carriers suggested significant differences of the three genotypes of PSEN2 promoter between AD and controls （ P = 0. 038）. Logistic analyses indicated ApoE genotypes were related with AD, and after stratification by ε4 allele, PSEN2 genotypes were related with AD of ε4 non-carriers. In addition, there was no interaction between ApoE and PSEN2 gene. Conclusion The ＋ A/- A polymorphism of PSEN2 promoter may be a minor genetic risk factor for sporadic AD, especially in the group of AD without ApoE ε4 allele.
出处
《中华神经科杂志》
CAS
CSCD
北大核心
2007年第1期18-22,共5页
Chinese Journal of Neurology
