阿尔茨海默病CYP2D6*10基因多态性与多奈哌齐疗效

目的研究阿尔茨海默病（AD）患者CYP2D6＊10基因多态性对多奈哌齐疗效的影响。方法筛选AD患者110例（AD组）和健康体检者124例（对照组），应用限制性片段长度多态性一聚合酶链反应（RFLP—PCR）方法对两组患者进行CYP2D6＊10基因多态性测定。AD组给予多奈哌齐治疗6个月，于服药前后，应用简易精神状态量表（MMSE）和阿尔茨海默病评定量表认知分量表（ADAS-Cog）进行认知功能测定；应用高效液相色谱一质谱法测定患者血浆中多奈哌齐的稳态血药浓度。结果AD组与对照组CYP2D6＊10的基因型和等位基因频率分布差异无统计学意义（P〉0．05）；AD组CYP2D6＊10基因突变型（T/T型与C／T型）的血药浓度、MMSE和ADAS．Cog评分与野生型（C／C型）相比，差异均有统计学意义（P〈0．05）。结论多奈哌齐对阿尔茨海默病CYP2D6＊10基因突变型患者的疗效优于野生型患者。

CYP2D6*10 polymorphism and response to donepezil in patients with Alzheimer's disease

Objective To analyze the relation of CYP2D6＊10 polymorphism with response to donepezil in patients with Alzheimer＇s disease（AD）. Methods A total of 110 AD patients （AD group） and 124 healthy individuals （control group） were recruited for the study. RFLP-PCR was applied to analyze the CYP2D6＊10 gene polymorphisms. Besides, the AD patients were administrated with donepezil 5-10 mg/d for 6 months and evaluated by cognition scales （MMSE and ADAS-Cog） before and after therapy. The steady plasma concentration （Cp） of donepezil was measured by HPLC-MS. Results There was no statistical difference in genotypes and allele frequency of CYP2D6＊10 between AD group and control group. However, significant differences were found in AD patients on steady concentration of donepezil and cognition scores （MMSE and ADAS-Cog） between CYP2D6＊10 mutant genotypes （T/T and C/T group） and wild type （C/C group） （P 〈 0.05）. Conclusions Donepezil is more effective for AD patients carrying CYP2D6＊10 mutants than those carrying wild type.