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A single nucleotide polymorphism in CHAT influences response to acetylcholinesterase inhibitors in Alzheimer's disease

Harold, Denise, Macgregor, S., Patterson, C. E., Hollingworth, P., Moore, P., Owen, Michael John, Williams, Julie, O'Donovan, Michael Conlon, Passmore, P., McIlroy, S. and Jones, Lesley 2006. A single nucleotide polymorphism in CHAT influences response to acetylcholinesterase inhibitors in Alzheimer's disease. Pharmacogenetics and genomics 16 (2) , pp. 75-77.

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Abstract

Background Alzheimer's disease ( AD) is a devastating neurodegeneration with a characteristic deficit in cholinergic neurotransmission. Treatment with acetylcholinesterase ( AChE) inhibitors aims to reverse this deficit and does ameliorate the decline in cognition in some AD patients, although response is variable. Objective To examine whether sequence variation in the gene encoding choline acetyltransferase ( CHAT), which encodes the major catalytic enzyme of the cholinergic pathway, predicts response to AChE inhibitors. Methods Alzheimer's disease patients ( 121) were treated with cholinesterase inhibitors and the effect of treatment on cognition was measured using the Mini Mental State Examination ( MMSE). Six polymorphisms in CHAT were analysed for association with change in MMSE score. Results After correction for multiple testing, we found one SNP, rs733722, in a promoter region of CHAT, is associated with response of AD patients to cholinesterase inhibitors ( P = 0.03) and accounts for 6% of the variance in response to AChE inhibitors. Conclusion Rs733722 represents a putative marker of response to AChE inhibitors in AD patients.

Item Type: Article
Date Type: Publication
Status: Published
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Medicine
Publisher: Lippincott Williams & Wilkins
ISSN: 1744-6872
Last Modified: 25 Dec 2017 20:43
URI: http://orca.cf.ac.uk/id/eprint/82966

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