阿尔茨海默病CYP2D6*10基因多态性与多奈哌齐疗效

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

摘要:

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-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-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。

Abstract:

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 ad ministrated 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.