title: 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.
authors.affiliation: Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Ashare
authors.forename: J H
authors.initials: JH
authors.lastname: Karlawish
authors.forename: E P
authors.initials: EP
authors.lastname: Wileyto
authors.forename: A
authors.initials: A
authors.lastname: Pinto
authors.forename: C
authors.initials: C
authors.lastname: Lerman
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D016540:Smoking Cessation; D055815:Young Adult
chemical_list: D053327:Apolipoprotein E4