The Effect of Choline Acetyltransferase Genotype on Donepezil Treatment Response in Patients with Alzheimer’s Disease
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Objective: We examined the difference in responses to donepezil between carriers and non-carriers of the A allele at the +4 position of the choline acetyltransferase (ChAT) gene in Koreans. Methods: Patients who met the criteria for probable Alzheimer’s disease (AD) (n=199) were recruited. Among these, 145 completed the 12-week follow-up evaluation and 135 completed the 26-week scheduled course. Differences and changes in the Korean version of the mini-mental state examination (MMSE-KC) score, Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease Neuropsychological Assessment Battery (CERAD-K[N]) wordlist subtest score (WSS), CERAD-K(N) total score (TS), and the Korean version of geriatric depression scale (GDS-K) score between baseline and 12 weeks or 26 weeks were assessed by the Student’s t-test. Results: At 12 weeks, the changes in the MMSE-KC score, CERAD-K(N) WSS, and CERAD-K(N) TS from baseline were not significant between ChAT A allele carriers and non-carriers; however, at 26 weeks, these changes were significantly larger in ChAT A allele carriers than in non-carriers (p=0.02 for MMSE-KC and p=0.03 for CERAD-K(N) WSS respectively). Conclusion: Our findings in this study suggested that presence of the A allele at the +4 position of ChAT might positively influence the treatment effect of donepezil in the early stages of AD in Koreans.
Abstract
Objective: We examined the difference in responses to donepezil between carriers and non-carriers of the A allele at the +4 position of the choline acetyltransferase (ChAT) gene in Koreans. Methods: Patients who met the criteria for probable Alzheimer’s disease (AD) (n=199) were recruited. Among these, 145 completed the 12-week follow-up evaluation and 135 completed the 26-week scheduled course. Differences and changes in the Korean version of the mini-mental state examination (MMSE-KC) score, Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease Neuropsychological Assessment Battery (CERAD-K[N]) wordlist subtest score (WSS), CERAD-K(N) total score (TS), and the Korean version of geriatric depression scale (GDS-K) score between baseline and 12 weeks or 26 weeks were assessed by the Student’s t-test. Results: At 12 weeks, the changes in the MMSE-KC score, CERAD-K(N) WSS, and CERAD-K(N) TS from baseline were not significant between ChAT A allele carriers and non-carriers; however, at 26 weeks, these changes were significantly larger in ChAT A allele carriers than in non-carriers (p=0.02 for MMSE-KC and p=0.03 for CERAD-K(N) WSS respectively). Conclusion: Our findings in this study suggested that presence of the A allele at the +4 position of ChAT might positively influence the treatment effect of donepezil in the early stages of AD in Koreans.
참고문헌 (32)
- Birks J., "Cholinesterase inhibitors for Alzheimer's disease", Cochrane Database Syst Rev, (1), pp.CD005593~ (2006)
- Hansen RA., "Functional outcomes of drug treatment in Alzheimer's disease : A systematic review and meta-analysis", Drugs Aging, 24, pp.155~167 (2007)
- Jann MW., "Clinical pharmacokinetics and pharmacodynamics of cholinesterase inhibitors", Clin Pharmacokinet, 41, pp.719~739 (2002)
- Cacabelos R., "Pharmacogenomic protocols in CNS disorders Cacabelos R, Martínez R, Fernández-Novoa L, Carril JC, Lombardi V, Carrera I, et al. Genomics of Dementia : APOEand CYP2D6-Related Pharmacogenetics", Int J Alzheimers Dis, 2012, pp.518901~ (2012)
- Pilotto A., "Effect of a CYP2D6 polymorphism on the efficacy of donepezil in patients with Alzheimer disease", Neurology, 73, pp.761~767 (2009)
- Seripa D., "Role of cytochrome P4502D6 functional polymorphisms in the efficacy of donepezil in patients with Alzheimer's disease", Pharmacogenet Genomics, 21, pp.225~230 (2011)
- Varsaldi F., "Impact of the CYP2D6 polymorphism on steady-state plasma concentrations and clinical outcome of donepezil in Alzheimer's disease patients", Eur J Clin Pharmacol, 62, pp.721~726 (2006)
- Bizzarro A., "Apolipoprotein E epsilon4 allele differentiates the clinical response to donepezil in Alzheimer's disease", Dement Geriatr Cogn Disord, 20, pp.254~261 (2005)
- Choi SH., "Effect of ApoE genotype on response to donepezil in patients with Alzheimer's disease", Dement Geriatr Cogn Disord, 25, pp.445~450 (2008)
- Rigaud AS., "Presence or absence of at least one epsilon 4 allele and gender are not predictive for the response to donepezil treatment in Alzheimer's disease", Pharmacogenetics, 12, pp.415~420 (2002)
- Harold D., "A single nucleotide polymorphism in CHAT influences response to acetylcholinesterase inhibitors in Alzheimer's disease", Pharmacogenet Genomics, 16, pp.75~77 (2006)
- Davies P., "Neurotransmitter-related enzymes in senile dementia of the Alzheimer type", Brain Res, 171, pp.319~327 (1979)
- Wilcock GK., "Alzheimer's disease. Correlation of cortical choline acetyltransferase activity with the severity of dementia and histological abnormalities", J Neurol Sci, 57, pp.407~417 (1982)
- Kozak M., "Recognition of AUG and alternative initiator codons is augmented by G in position +4 but is not generally affected by the nucleotides in positions +5 and +6", EMBO J, 16, pp.2482~2492 (1997)
- Lee JJ., "Choline acetyltransferase 2384G>a polymorphism and the risk of Alzheimer disease", Alzheimer Dis Assoc Disord, 26, pp.81~87 (2012)
- Ahn Jo S., "ApoE-epsilon 4-dependent association of the choline acetyltransferase gene polymorphisms(2384G>A and 1882G>A)with Alzheimer's disease", Clin Chim Acta, 368, pp.179~182 (2006)
- Kim KW., "Choline acetyltransferase G +4 A polymorphism confers a risk for Alzheimer's disease in concert with Apolipoprotein E epsilon4", Neurosci Lett, 366, pp.182~186 (2004)
- Scacchi R., "Variability of AChE, BChE, and ChAT genes in the late-onset form of Alzheimer's disease and relationships with response to treatment with Donepezil and Rivastigmine", Am J Med Genet B Neuropsychiatr Genet, 150B, pp.502~507 (2009)
- McKhann G., "Clinical diagnosis of Alzheimer's disease : report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease", Neurology, 34, pp.939~944 (1984)
- Morris JC., "The Clinical Dementia Rating(CDR) : current version and scoring rules", Neurology, 43, pp.2412~2414 (1993)
- Rosen WG., "Pathological verification of ischemic score in differentiation of dementias", Ann Neurol, 7, pp.486~488 (1980)
- Lee DY., "A normative study of the CERAD neuropsychological assessment battery in the Korean elderly", J Int Neuropsychol Soc, 10, pp.72~81 (2004)
- Bae JN., "Development of the Korean version of the Geriatric Depression Scale and its short form among elderly psychiatric patients", J Psychosom Res, 57, pp.297~305 (2004)
- Sotaniemi M., "CERAD-neuropsychological battery in screening mild Alzheimer's disease", Acta Neurol Scand, 125, pp.16~23 (2012)
- Chandler MJ., "A total score for the CERAD neuropsychological battery", Neurology, 65, pp.102~106 (2005)
- Park HD., "Real-time multiplex PCR assay for genotyping of three apolipoprotein E alleles and two choline acetyltransferase alleles with three hybridization probes", Clin Chem Lab Med, 45, pp.346~350 (2007)
- Kim KW., "Association between apolipoprotein E polymorphism and Alzheimer's disease in Koreans", Neurosci Lett, 277, pp.145~148 (1999)
- DeKosky ST., "Cortical biopsy in Alzheimer's disease : diagnostic accuracy and neurochemical, neuropathological, and cognitive correlations. Intraventricular Bethanecol Study Group", Ann Neurol, 32, pp.625~632 (1992)
- Tang M., "Evaluation of choline acetyltransferase gene polymorphism(2384 G", A)in Alzheimer's disease and mild cognitive impairment, 2008, pp.26, 9~14
- Harold D., "Sequence variation in the CHAT locus shows no association with late-onset Alzheimer's disease", Hum Genet, 113, pp.258~267 (2003)
- Schwarz S., "Lack of association between a single nucleotide polymorphism within the choline acetyltransferase gene and patients with Alzheimer's disease", Neurosci Lett, 343, pp.167~170 (2003)
- Haubrich DR., "Regulation of acetylcholine synthesis in nervous tissue", Life Sci, 20, pp.1465~1478 (1977)
