title: CHRNA7 Polymorphisms and Dementia Risk: Interactions with Apolipoprotein ε4 and Cigarette Smoking.
abstract: α7 nicotinic acetylcholine receptor (α7nAChR, encoded by CHRNA7) is involved in dementia pathogenesis through cholinergic neurotransmission, neuroprotection and interactions with amyloid-β. Smoking promotes atherosclerosis and increases dementia risk, but nicotine exerts neuroprotective effect via α7nAChR in preclinical studies. No studies explored the gene-gene, gene-environment interactions between CHRNA7 polymorphism, apolipoprotein E (APOE) ε4 status and smoking on dementia risk. This case-control study recruited 254 late-onset Alzheimer's disease (LOAD) and 115 vascular dementia (VaD) cases (age ≥65) from the neurology clinics of three teaching hospitals in Taiwan during 2007-2010. Controls (N = 435) were recruited from health checkup programs and volunteers during the same period. Nine CHRNA7 haplotype-tagging single nucleotide polymorphisms representative for Taiwanese were genotyped. Among APOE ε4 non-carriers, CHRNA7 rs7179008 variant carriers had significantly decreased LOAD risk after correction for multiple tests (GG + AG vs. AA: adjusted odds ratio = 0.29, 95% confidence interval = 0.13-0.64, P = 0.002). Similar findings were observed for carriers of GT haplotype in CHRNA7 block4. A significant interaction was found between rs7179008, GT haplotype in block4 and APOE ε4 on LOAD risk. rs7179008 variant also reduced the detrimental effect of smoking on LOAD risk. No significant association was found between CHRNA7 and VaD. These findings help to understand dementia pathogenesis.
authors.affiliation: Department of Family Medicine, Taiwan Adventist Hospital, Taipei, Taiwan.|Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
authors.forename: Pei-Hsuan
authors.initials: PH
authors.lastname: Weng
authors.affiliation: 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.
authors.forename: Jen-Hau
authors.initials: JH
authors.lastname: Chen
authors.affiliation: Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Ta-Fu
authors.initials: TF
authors.lastname: Chen
authors.affiliation: Department of Neurology, En Chu Kong Hospital, New Taipei City, Taiwan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Laboratory Medicine, En Chu Kong Hospital, New Taipei City, Taiwan.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Wen
authors.affiliation: School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan.|Center of Neurological Medicine, Cardinal Tien Hospital, New Taipei City, Taiwan.
authors.forename: Ping-Keung
authors.initials: PK
authors.lastname: Yip
authors.affiliation: Department of Laboratory Medicine, Cardinal Tien Hospital, New Taipei City, Taiwan.
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: Chu
authors.affiliation: 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.
authors.forename: Yen-Ching
authors.initials: YC
authors.lastname: Chen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D016022:Case-Control Studies; D000073865:Cigarette Smoking; D015140:Dementia, Vascular / Q000235:genetics*; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000235:genetics*
chemical_list: C000612345:ApoE protein, human; D001057:Apolipoproteins E; C579167:Chrna7 protein, human; D064569:alpha7 Nicotinic Acetylcholine Receptor