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Interleukin-1beta Promoter Polymorphism Enhances the Risk of Sleep Disturbance in Alzheimer's Disease.

Authors: Yin, Y  Liu, Y  Pan, X  Chen, R  Li, P  Wu, HJ  Zhao, ZQ  Li, YP  Huang, LQ  Zhuang, JH  Zhao, ZX 
Citation: Yin Y, etal., PLoS One. 2016 Mar 3;11(3):e0149945. doi: 10.1371/journal.pone.0149945. eCollection 2016.
Pubmed: (View Article at PubMed) PMID:26937653
DOI: Full-text: DOI:10.1371/journal.pone.0149945

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)-1beta and APOEepsilon4 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-1beta and APOEepsilon4 SNPs using ligase detection reaction (LDR) technology. Blood levels of IL-1beta, IL-6, and tumor necrosis factor alpha (TNF-alpha) 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-APOEepsilon4/epsilon4 genotype, APOEepsilon4/epsilon4 significantly increased the risk of AD (APOEepsilon4/epsilon4 vs. non-APOEepsilon4/epsilon4, adjusted OR = 4.33, 95% CI = 1.33-14.10, p = 0.015). Compared to the IL-1beta 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 APOEepsilon4 allele and the IL-1beta 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-1beta levels were significantly greater in AD patients carrying both the APOEepsilon4 allele and the IL-1beta-31TT genotype than in those carrying the APOEepsilon4 allele and the -31 TC or CC genotype. In conclusion, this study provides the first evidence indicating that the IL-1beta-31TT genotype and homozygous APOEepsilon4 combined are associated with increased risk of developing AD with sleep disturbance.

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CRRD Object Information
CRRD ID: 11522340
Created: 2016-08-03
Species: All species
Last Modified: 2016-08-03
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.