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Presence of the apolipoprotein E-?4 allele is associated with an increased risk of sepsis progression.

ABSTRACT: Growing evidence indicated that single nucleotide polymorphisms (SNPs) in the apolipoprotein E (APOE) gene are related to increase the risk of many inflammatory-related diseases. However, few genetic studies have associated the APOE gene polymorphism with sepsis. This study was to investigate the clinical relevance of the APOE gene polymorphism in the onset and progression of sepsis. A multicenter case-control association study with a large sample size (601 septic patients and 699 healthy individuals) was conducted. Clinical data showed that the APOE?4 allele was overrepresented among all patients with septic shock (p?=?0.031) compared with sepsis subtype, suggesting that APOE?4 allele may associated with increased susceptibility to the progression of sepsis. Moreover, the APOE mRNA levels decreased after lipopolysaccharide (LPS) stimulation in cells in culture. Then 21 healthy individuals to extract PBMC for genotype grouping (APOE4+ group 8; APOE4- group 13) was selected to evaluate the effect on APOE level, and results showed that the expression level of APOE in APOE4+ group and APOE4- group did not differ in mRNA levels after an LPS challenge, but the protein levels in APOE4+ group decreased slower than that in APOE4- group, and this process was accompanied by the upregulation of proinflammatory cytokines. These results provide evidence that the APOE?4 allele might be associated with the development of sepsis and a potential risk factor that can be used in the prognosis of sepsis.

SUBMITTER: Shao Y

PROVIDER: S-EPMC7519096 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Presence of the apolipoprotein E-ε4 allele is associated with an increased risk of sepsis progression.

Shao Yiming Y Zhao Tian T Zhang Wenying W He Junbing J Lu Furong F Cai Yujie Y Lai Zhipeng Z Wei Ning N Liang Chunmei C Liu Lizhen L Hong Yuan Y Cheng Xiaohong X Li Jia J Tang Pei P Fan Weihao W Ou Mingqian M Yang Jingqi J Liu Yansong Y Cui Lili L

Scientific reports 20200925 1

Growing evidence indicated that single nucleotide polymorphisms (SNPs) in the apolipoprotein E (APOE) gene are related to increase the risk of many inflammatory-related diseases. However, few genetic studies have associated the APOE gene polymorphism with sepsis. This study was to investigate the clinical relevance of the APOE gene polymorphism in the onset and progression of sepsis. A multicenter case-control association study with a large sample size (601 septic patients and 699 healthy indivi ...[more]

PMID: 32978453

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Project description:ImportanceThe apolipoprotein E (APOE [GenBank, 348; OMIM, 107741]) ε4 allele is a common and well-established genetic risk factor for Alzheimer disease (AD). Sleep consolidation is also associated with AD risk, and previous work suggests that APOE genotype and sleep may interact to influence cognitive function.ObjectiveTo determine whether better sleep consolidation attenuates the relationship of the APOE genotype to the risk of incident AD and the burden of AD pathology.Design, setting, and participantsA prospective longitudinal cohort study with up to 6 years of follow-up was conducted. Participants included 698 community-dwelling older adults without dementia (mean age, 81.7 years; 77% women) in the Rush Memory and Aging Project.ExposuresWe used up to 10 days of actigraphic recording to quantify the degree of sleep consolidation and ascertained APOE genotype.Main outcomes and measuresParticipants underwent annual evaluation for AD during a follow-up period of up to 6 years. Autopsies were performed on 201 participants who died, and β-amyloid (Aβ) and neurofibrillary tangles were identified by immunohistochemistry and quantified.ResultsDuring the follow-up period, 98 individuals developed AD. In a series of Cox proportional hazards regression models, better sleep consolidation attenuated the effect of the ε4 allele on the risk of incident AD (hazard ratio, 0.67; 95% CI, 0.46-0.97; P = .04 per allele per 1-SD increase in sleep consolidation). In a series of linear mixed-effect models, better sleep consolidation also attenuated the effect of the ε4 allele on the annual rate of cognitive decline. In individuals who died, better sleep consolidation attenuated the effect of the ε4 allele on neurofibrillary tangle density (interaction estimate, -0.42; SE = 0.17; P = .02), which accounted for the effect of sleep consolidation on the association between APOE genotype and cognition proximate to death.Conclusions and relevanceBetter sleep consolidation attenuates the effect of APOE genotype on incident AD and development of neurofibrillary tangle pathology. Assessment of sleep consolidation may identify APOE+ individuals at high risk for incident AD, and interventions to enhance sleep consolidation should be studied as potentially useful means to reduce the risk of AD and development of neurofibrillary tangles in APOE ε4+ individuals.

Dataset Information

Presence of the apolipoprotein E-?4 allele is associated with an increased risk of sepsis progression.

Publications

Presence of the apolipoprotein E-ε4 allele is associated with an increased risk of sepsis progression.

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