Association of CHAT Gene Polymorphism rs3793790 and rs2177370 with Donepezil Response and the Risk of Alzheimer’s Disease Continuum

Abstract

Hongmei Sun,1,2 Chao Lv,2,3 Xiaoxue Zhang,1,2 Xuan Sun,1,3,4 Siyu Chen,1,3,4 Ke Li,3,4 Yazhuo Hu,2,3 Yuxin Feng,1,2 Tong Yin,2,3 Jianjun Jia2,3 1Medical School, Chinese PLA General Hospital, Beijing, People’s Republic of China; 2Institute of Geriatrics, Chinese PLA General Hospital, Beijing, People’s Republic of China; 3National Clinical Research Center of Geriatric Diseases, Chinese PLA General Hospital, Beijing, People’s Republic of China; 4Department of Geriatric Neurology, the Second Medical Centre, Chinese PLA General Hospital, Beijing, People’s Republic of ChinaCorrespondence: Jianjun Jia; Tong Yin, Institute of Geriatrics, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, Haidian District, 100853, People’s Republic of China, Email [email protected]; [email protected]: Genetic variation plays an important role in drug response, there are few relevant studies on patients with Alzheimer’s disease continuum (ADC).Objective: 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.Material and Methods: 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.Results: 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).Conclusion: 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.Keywords: Alzheimer’s disease, pharmacogenomics, variant, gene, donepezil

Keywords

• alzheimer’s disease
• pharmacogenomics
• variant
• gene
• donepezil