title: Interleukin-1β Promoter Polymorphism Enhances the Risk of Sleep Disturbance in Alzheimer's Disease.
abstract: Sleep alleviates Alzheimer's disease (AD)-related neuropathological processes, whereas sleep disturbance in AD patients is associated with elevated peripheral inflammatory cytokine levels. In the present study, we assessed interleukin (IL)-1β and APOEε4 polymorphisms for association with susceptibility of sleep disturbances in AD patients. A total of 123 pretreated AD patients and 120 age-, gender- and education level-matched healthy controls were recruited for two consecutive full-night polysomnography and measurement of Epworth Sleepiness Scale (ESS) scores for sleep-wake disturbance. Their genomic DNA was analyzed for IL-1β and APOEε4 SNPs using ligase detection reaction (LDR) technology. Blood levels of IL-1β, IL-6, and tumor necrosis factor alpha (TNF-α) were measured using ELISA after lipopolysaccharide (LPS) stimulation. The odds ratio and 95% confidence interval for genotype-specific risk were calculated using an unconditional logistic regression model and adjusted by age, gender, educational levels, body mass index (BMI), and activities of daily living (ADL). Compared to the non-APOEε4/ε4 genotype, APOEε4/ε4 significantly increased the risk of AD (APOEε4/ε4 vs. non-APOEε4/ε4, adjusted OR = 4.33, 95% CI = 1.33-14.10, p = 0.015). Compared to the IL-1β CC genotype (-31), the TT genotype significantly increased the risk of AD (TT vs. CC, adjusted OR = 1.72, 95% CI = 1.13-2.61, p = 0.010). AD patients carrying the APOEε4 allele and the IL-1β TT genotype showed less time in bed, longer sleep latency and REM latency, more awakenings, and a lower SWS percentage than those carrying CC/CT combined genotypes. In addition, blood IL-1β levels were significantly greater in AD patients carrying both the APOEε4 allele and the IL-1β-31TT genotype than in those carrying the APOEε4 allele and the -31 TC or CC genotype. In conclusion, this study provides the first evidence indicating that the IL-1β-31TT genotype and homozygous APOEε4 combined are associated with increased risk of developing AD with sleep disturbance.
authors.affiliation: Department of Neurology, Changzheng Hospital, Second Military Medical University, Shanghai, China.|Institute of Neuroscience and MOE Key Laboratory of Molecular Neurobiology, Neuroscience Research Center of Changzheng Hospital, The Second Military Medical University Shanghai, Shanghai, China.
authors.forename: You
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Department of Pharmacy, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Neurology, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Pan
authors.affiliation: Department of Neurology, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Neurology, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Neurology, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Hui-Juan
authors.initials: HJ
authors.lastname: Wu
authors.affiliation: Department of Neurology, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Zheng-Qing
authors.initials: ZQ
authors.lastname: Zhao
authors.affiliation: Department of Neurology, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Yan-Peng
authors.initials: YP
authors.lastname: Li
authors.affiliation: Department of Neurology, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Liu-Qing
authors.initials: LQ
authors.lastname: Huang
authors.affiliation: Department of Neurology, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Zhuang
authors.affiliation: Department of Neurology, Changzheng Hospital, Second Military Medical University, Shanghai, China.|Institute of Neuroscience and MOE Key Laboratory of Molecular Neurobiology, Neuroscience Research Center of Changzheng Hospital, The Second Military Medical University Shanghai, Shanghai, China.
authors.forename: Zhong-Xin
authors.initials: ZX
authors.lastname: Zhao
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012893:Sleep Wake Disorders / Q000235:genetics*
chemical_list: D053327:Apolipoprotein E4; C508585:IL1B protein, human; D053583:Interleukin-1beta; D008070:Lipopolysaccharides