Medical School, Chinese PLA General Hospital, Beijing, People's Republic of China.
Institute of Geriatrics, Chinese PLA General Hospital, Beijing, People's Republic of China.
Clin Interv Aging. 2024 Jun 11;19:1041-1050. doi: 10.2147/CIA.S462786. eCollection 2024.
Genetic variation plays an important role in drug response, there are few relevant studies on patients with Alzheimer's disease continuum (ADC).
This study focused on the associations between two single nucleotide polymorphisms (SNPs) (rs3793790 and rs2177370) located in the CHAT gene and donepezil response in ADC patients, and further evaluated the associations between the two SNPs and ADC.
According to 2018 National Institute on Aging and Alzheimer's Association (NIA-AA) standard, amyloid β-protein positive (Aβ+) and negative (Aβ-) patients were recruited according to the Aβ-PET/CT standard. rs3793790 and rs2177370 were genotyped in buccal swab samples by using the MassARRAY system. We used the Mini Mental State Examination (MMSE) in Chinese version, caregiver evaluation, and prescribing behavior to assess therapeutic response during the 9-month period. Using logistic regression models, we analyzed the relationship between the two SNPs and donepezil response in 58 Aβ+ patients treated with donepezil alone at the initial diagnosis of ADC. We also explored a probable link between the two SNPs and ADC in 147 Aβ+ and 73 Aβ- patients using a logistic regression analysis.
The chance of donepezil response was higher in patients with the G allele of rs3793790 and/or the A allele of rs2177370 than in those without (odds ratio (OR) 6.83, 95% confidence interval (CI): 1.64-28.49). Additionally, the rs3793790 variant was not associated with ADC, whereas the A allele in rs2177370 increased 1.51-fold the ADC risk (OR 2.51, 95% CI: 1.28-4.95).
The genetic variants of rs3793790 and rs2177370 were associated with the donepezil response, and rs2177370 may have a moderate relationship with the risk of ADC.
遗传变异在药物反应中起着重要作用，而针对阿尔茨海默病连续体（ADC）患者的相关研究较少。
本研究主要关注位于 CHAT 基因中的两个单核苷酸多态性（SNP）（rs3793790 和 rs2177370）与 ADC 患者使用多奈哌齐的反应之间的关系，并进一步评估这两个 SNP 与 ADC 的关系。
根据 2018 年美国国家老龄化研究所和阿尔茨海默病协会（NIA-AA）标准，根据 Aβ-PET/CT 标准，按淀粉样β蛋白阳性（Aβ+）和阴性（Aβ-）招募患者。使用 MassARRAY 系统，通过颊拭子样本检测 rs3793790 和 rs2177370 的基因型。我们使用中文版简易精神状态检查（MMSE）、照料者评估和处方行为，在 ADC 初诊时评估 9 个月期间的治疗反应。使用逻辑回归模型，我们分析了在 58 名 Aβ+患者中，这两个 SNP 与单独使用多奈哌齐治疗的关系。我们还使用逻辑回归分析，在 147 名 Aβ+和 73 名 Aβ-患者中，探索了这两个 SNP 与 ADC 之间的可能联系。
与没有携带 rs3793790 的 G 等位基因和/或 rs2177370 的 A 等位基因的患者相比，携带 rs3793790 的 G 等位基因和/或 rs2177370 的 A 等位基因的患者多奈哌齐反应的几率更高（比值比（OR）6.83，95%置信区间（CI）：1.64-28.49）。此外，rs3793790 变异与 ADC 无关，而 rs2177370 中的 A 等位基因使 ADC 风险增加 1.51 倍（OR 2.51，95%CI：1.28-4.95）。
rs3793790 和 rs2177370 的遗传变异与多奈哌齐的反应有关，rs2177370 可能与 ADC 的风险有一定的关系。
