A bioinformatics driven map of pharmacogenomic variation and genetic variants in Alzheimer’s disease therapy
https://doi.org/10.14412/2074-2711-2025-6-61-68
Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that is the leading cause of dementia globally. First-line AD therapy using cholinesterase inhibitors such as donepezil, galantamine, and rivastigmine shows interindividual variation in effectiveness, indicating the involvement of genetic factors. This study aims to identify genetic variants that influence response to AD therapy through bioinformatics and pharmacogenomic approaches. Data were retrieved from PharmGKB and analyzed based on therapy efficacy, allele frequencies across populations (1000 Genomes), and gene expression (GTEx). Four SNP variants were found to be relevant: rs6494223 (CHRNA7), rs3793790 and rs2177370 (CHAT), and rs1803274 (BCHE). Specific genotypes such as CC (rs6494223), GG and AA (CHAT), and TT (rs1803274) showed better therapy response. Expression analysis showed that the CHAT gene is highly expressed in the brain, reinforcing its pharmacogenetic relevance. In contrast, CHRNA7 and BCHE showed high expression in non-neuronal tissues, yet still play a systemic role in acetylcholine metabolism. Variations in allele frequencies between populations were also identified, underscoring the importance of population-based therapeutic approaches. These results support the importance of simple genetic screening in the development of precision therapies for Alzheimer’s. This study demonstrates that integrating pharmacogenomic and gene expression data can provide a better understanding of the heterogeneity of AD therapy response and open the possibility of personalized treatment based on the patient’s genetic profile.
Supporting agencies: The investigation has not been sponsored
About the Authors
D. P. Amukti
Alma Ata University
Indonesia
Competing Interests:
Indonesia
Danang Prasetyaning Amukti - Department of Pharmacy, Faculty of Medicine and Health Science.
Jl. Brawijaya No.99, Tamantirto, Kasihan, Bantul, Yogyakarta, 55183
Competing Interests:
There are no conflicts of interest
N. Kusumawardani
Alma Ata University
Indonesia
Competing Interests:
Indonesia
Jl. Brawijaya No.99, Tamantirto, Kasihan, Bantul, Yogyakarta, 55183
Competing Interests:
There are no conflicts of interest
D. Estiningsih
Alma Ata University
Indonesia
Competing Interests:
Indonesia
Jl. Brawijaya No.99, Tamantirto, Kasihan, Bantul, Yogyakarta, 55183
Competing Interests:
There are no conflicts of interest
T. Herlina
Alma Ata University
Indonesia
Competing Interests:
Indonesia
Jl. Brawijaya No.99, Tamantirto, Kasihan, Bantul, Yogyakarta, 55183
Competing Interests:
There are no conflicts of interest
E. Nurinda
Alma Ata University
Indonesia
Competing Interests:
Indonesia
Jl. Brawijaya No.99, Tamantirto, Kasihan, Bantul, Yogyakarta, 55183
Competing Interests:
There are no conflicts of interest
R. Indah Pratami
Ahmad Dahlan University
Indonesia
Competing Interests:
Indonesia
Faculty of Pharmacy.
Jl. Kapas 9, Semaki, Umbulharjo, Yogyakarta 55166
Competing Interests:
There are no conflicts of interest
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For citations:
Amukti DP, Kusumawardani N, Estiningsih D, Herlina T, Nurinda E, Indah Pratami R. A bioinformatics driven map of pharmacogenomic variation and genetic variants in Alzheimer’s disease therapy. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2025;17(6):61-68. https://doi.org/10.14412/2074-2711-2025-6-61-68
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