CHRNA7 polymorphisms and response to cholinesterase inhibitors in Alzheimer's disease

Pei-Hsuan Weng; Jen-Hau Chen; Ta-Fu Chen; Yu Sun; Li-Li Wen; Ping-Keung Yip; Yi-Min Chu; Yen-Ching Chen

doi:10.1371/journal.pone.0084059

CHRNA7 polymorphisms and response to cholinesterase inhibitors in Alzheimer's disease

PLoS One. 2013 Dec 31;8(12):e84059. doi: 10.1371/journal.pone.0084059. eCollection 2013.

Authors

Pei-Hsuan Weng¹, Jen-Hau Chen², Ta-Fu Chen³, Yu Sun⁴, Li-Li Wen⁵, Ping-Keung Yip⁶, Yi-Min Chu⁷, Yen-Ching Chen⁸

Affiliations

¹ Department of Family Medicine, Taiwan Adventist Hospital, Taipei, Taiwan ; Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
² Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan ; Department of Geriatrics and Gerontology, National Taiwan University Hospital, Taipei, Taiwan.
³ Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan.
⁴ Department of Neurology, En Chu Kong Hospital, Taipei, Taiwan.
⁵ Department of Laboratory Medicine, En Chu Kong Hospital, Taipei, Taiwan.
⁶ Center of Neurological Medicine, Cardinal Tien Hospital, Taipei, Taiwan ; School of Medicine, Fu-Jen Catholic University, Taipei, Taiwan.
⁷ Department of Laboratory Medicine, Cardinal Tien Hospital, Taipei, Taiwan.
⁸ Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan ; Department of Public Health, College of Public Health, National Taiwan University, Taipei, Taiwan ; Research Center for Genes, Environment and Human Health, College of Public Health, National Taiwan University, Taipei, Taiwan.

Abstract

Background: CHRNA7 encodes the α7 nicotinic acetylcholine receptor subunit, which is important to Alzheimer's disease (AD) pathogenesis and cholinergic neurotransmission. Previously, CHRNA7 polymorphisms have not been related to cholinesterase inhibitors (ChEI) response.

Methods: Mild to moderate AD patients received ChEIs were recruited from the neurology clinics of three teaching hospitals from 2007 to 2010 (n = 204). Nine haplotype-tagging single nucleotide polymorphisms of CHRNA7 were genotyped. Cognitive responders were those showing improvement in the Mini-Mental State Examination score ≥ 2 between baseline and 6 months after ChEI treatment.

Results: AD women carrying rs8024987 variants [GG+GC vs. CC: adjusted odds ratio (AOR) = 3.62, 95% confidence interval (CI) = 1.47-8.89] and GG haplotype in block1 (AOR = 3.34, 95% CI = 1.38-8.06) had significantly better response to ChEIs (false discovery rate <0.05). These variant carriers using galantamine were 11 times more likely to be responders than female non-carriers using donepezil or rivastigmine.

Conclusion: For the first time, this study found a significant association between CHRNA7 polymorphisms and better ChEI response. If confirmed by further studies, CHRNA7 polymorphisms may aid in predicting ChEI response and refining treatment choice.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Alzheimer Disease / complications
Alzheimer Disease / drug therapy
Alzheimer Disease / genetics*
Cholinesterase Inhibitors / therapeutic use*
Cognition Disorders / diagnosis
Cognition Disorders / etiology
Female
Follow-Up Studies
Genotype
Haplotypes / genetics*
Humans
Male
Middle Aged
Polymorphism, Genetic / genetics*
Prognosis
Retrospective Studies
alpha7 Nicotinic Acetylcholine Receptor / genetics*

Substances

Cholinesterase Inhibitors
Chrna7 protein, human
alpha7 Nicotinic Acetylcholine Receptor

Grants and funding

Funding for the study was provided by National Science Council grants 96-2314-B-002-197 and 97-2314-B-002-168-MY3. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.