https://scholars.lib.ntu.edu.tw/handle/123456789/519472
標題: | CHRNA7 Polymorphisms and Dementia Risk: Interactions with Apolipoprotein ε4 and Cigarette Smoking | 作者: | Weng, Pei-Hsuan JEN-HAU CHEN TA-FU CHEN Sun, Yu Wen, Li-Li Yip, Ping-Keung Chu, Yi-Min YEN-CHING CHEN |
公開日期: | 2016 | 出版社: | Nature Publishing Group | 卷: | 6 | 起(迄)頁: | 27231 | 來源出版物: | Scientific Reports | 摘要: | 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) ?4 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 ?4 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 ?4 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. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84973326559&doi=10.1038%2fsrep27231&partnerID=40&md5=6f07f2ac45deefdac25159ee6919fb58 https://scholars.lib.ntu.edu.tw/handle/123456789/519472 |
ISSN: | 2045-2322 | DOI: | 10.1038/srep27231 | SDG/關鍵字: | ApoE protein, human; apolipoprotein E; bungarotoxin receptor; Chrna7 protein, human; aged; Alzheimer disease; case control study; cigarette smoking; female; genetic predisposition; genetics; genotype environment interaction; human; male; multiinfarct dementia; odds ratio; single nucleotide polymorphism; very elderly; Aged; Aged, 80 and over; alpha7 Nicotinic Acetylcholine Receptor; Alzheimer Disease; Apolipoproteins E; Case-Control Studies; Cigarette Smoking; Dementia, Vascular; Female; Gene-Environment Interaction; Genetic Predisposition to Disease; Humans; Male; Odds Ratio; Polymorphism, Single Nucleotide |
顯示於: | 醫學系 |
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