Effect of CYP2D6 and CYP3A4 Genotypes on the Efficacy of Cholinesterase Inhibitors in Southern Chinese Patients With Alzheimer's Disease.

Abstract	Alzheimer's disease (AD) is the most prevalent form of dementia, and age is strongly associated with the incidence of AD. This study aimed to investigate the association between the genotypes of CYP2D6, CYP3A4, and CYP2C9 genes to the clinical efficacy and tolerability of cholinesterase inhibitors (ChEIs) in Chinese patients with AD. One hundred seventy-nine patients with AD with newly prescribed with ChEIs were recruited. The clinical response and tolerability were evaluated at baseline, 3rd-, 6th-, and 12th-month follow-ups and were compared according to their genotypes of CYP2D6, CYP3A4, and CYP2C9. Among patients prescribed with donepezil/galantamine, CYP2D610 carriers showed significantly less side effects (P = .009). CYP2D610 carriers responded better to ChEIs and resulted in better improvement in Alzheimer's Disease Assessment Scale-Cognitive subscale (P = .027) and Mini-Mental State Examination (P = .012). Further study is required to replicate the finding, and it might be useful for clinicians to decide the medication based on the patients' CYP genotypes.
Authors	Suk Ling Ma, Nelson Leung Sang Tang, Karen Hong Yun Wat, Jenny Hoi Yin Tang, Ka Hin Lau, Chun Bon Law, John Chiu, Cindy Chi Woon Tam, Tin Keung Poon, Ka Leung Lin, Carolyn Poey Lyn Kng, Hing Leung Kong, Tak Yeung Chan, Wai Chi Chan, Linda Chiu Wa Lam
Journal	American journal of Alzheimer's disease and other dementias (Am J Alzheimers Dis Other Demen) Vol. 34 Issue 5 Pg. 302-307 (08 2019) ISSN: 1938-2731 [Electronic] United States
PMID	31064198 (Publication Type: Journal Article, Observational Study, Research Support, Non-U.S. Gov't)
Chemical References	Cholinesterase Inhibitors Galantamine Donepezil CYP2C9 protein, human Cytochrome P-450 CYP2C9 Cytochrome P-450 CYP2D6 Cytochrome P-450 CYP3A CYP3A4 protein, human Rivastigmine
Topics	Aged Aged, 80 and over Alzheimer Disease (drug therapy) Cholinesterase Inhibitors (adverse effects, pharmacology) Cytochrome P-450 CYP2C9 (genetics) Cytochrome P-450 CYP2D6 (genetics) Cytochrome P-450 CYP3A (genetics) Donepezil (adverse effects, pharmacology) Female Follow-Up Studies Galantamine (pharmacology) Genotype Hong Kong Humans Male Pharmacogenetics Pharmacogenomic Testing Rivastigmine (pharmacology)

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