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APOE ɛ4, an Alzheimer’s disease susceptibility allele, and smoking cessation

Abstract

Possessing an apolipoprotein E (APOE) ɛ4 allele, advanced age and smoking are risk factors for Alzheimer’s disease and cognitive decline. Deficits in cognitive function also increase risk for smoking relapse. Data from 917 adult smokers of European ancestry were pooled across three randomized trials of smoking cessation. We examined whether smokers who carry at least one ɛ4 allele (n=252) have more difficulty quitting smoking compared with noncarriers (n=665), and whether age moderated this association. The genotype by age interaction was significant for 7-day point-prevalence abstinence rates (P=0.04) and time to 7-day failure (P=0.03). Among smokers over age 60, ɛ4 carriers were less likely to quit (odds ratio=0.27, P=0.018) and relapsed more quickly (hazard ratio=3.38, P=0.001) compared with noncarriers. The genotype association with relapse was nonsignificant among younger smokers. An increased understanding of the underlying pathophysiological mechanisms of this association could facilitate the development of targeted therapies for smokers with increased risk for cognitive decline.

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Acknowledgements

The funding for this study was supported by P50 CA143187, U01 DA020830 and R01 DA030819 (Lerman). Dr Karlawish is supported by NIA P30AG01024. The NIH had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.

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Correspondence to C Lerman.

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Dr Lerman has served as a consultant and/or has received research funding from GlaxoSmithKline, AstraZeneca, Novartis and Pfizer. The current study was not supported by industry funds. Dr Wileyto has served as a consultant for Pfizer. The remaining authors declare no conflict of interest.

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Ashare, R., Karlawish, J., Wileyto, E. et al. APOE ɛ4, an Alzheimer’s disease susceptibility allele, and smoking cessation. Pharmacogenomics J 13, 538–543 (2013). https://doi.org/10.1038/tpj.2012.49

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Keywords

  • smoking
  • smoking cessation
  • relapse
  • nicotine
  • cognition
  • APOE

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