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

Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
The Pharmacogenomics Journal (Impact Factor: 5.51). 12/2012; DOI: 10.1038/tpj.2012.49
Source: PubMed

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.The Pharmacogenomics Journal advance online publication, 18 December 2012; doi:10.1038/tpj.2012.49.

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    ABSTRACT: Abstract Background: APOE e4 genotype is known to be a risk factor for Alzheimer's disease and atherosclerosis. Recently, published evidence has shown that APOE e4 genotype may also be associated with the cessation of cigarette smoking. Objectives: The aim of this retrospective analysis was to explore whether any past smoking outcomes differed based on APOE e4 genotype in a large national dataset. Methods: Data were extracted from the National Alzheimer's Coordinating Center's longitudinal Uniform Data Set study. We limited this retrospective baseline analysis to the normal cognition (n = 2995) and mild cognitive impairment (n = 1627) groups that had APOE genotype and smoking data. Because this was an exploratory retrospective analysis, we conducted descriptive analyses on all variables based on APOE e4 genotype. We controlled for demographic, clinical, medication and neurocognitive data in the analyses. Results: In both the normal cognition group and the mild cognitive impairment group, e4 carriers and e4 non-carriers did not significantly differ on total years smoked, age when last smoked and the average # of packs/day smoked during the years they smoked. In both groups, e4 carriers and e4 non-carriers differed on various neurocognitive measures. Conclusion: These data do not support the recently published evidence of the association between APOE e4 genotype and smoking outcomes. Scientific Significance: Larger prospective clinical trials are needed to further explore the relationship between APOE genotype and smoking outcomes.
    The American Journal of Drug and Alcohol Abuse 06/2013; DOI:10.3109/00952990.2013.800084 · 1.47 Impact Factor

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