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OncoTargets and Therapy 2016We conducted a systematic review and meta-analysis aiming to assess the relationship between apolipoprotein E (APOE) gene ε2/ε3/ε4 polymorphism and breast cancer risk.
OBJECTIVE
We conducted a systematic review and meta-analysis aiming to assess the relationship between apolipoprotein E (APOE) gene ε2/ε3/ε4 polymorphism and breast cancer risk.
METHODS
Yun-Long Liu and Hao-Min Zhang independently completed literature retrieval and data collection, and statistical analyses were performed by Stata. Individual odds ratio (OR) and 95% confidence interval (CI) were pooled in a random-effects model using the DerSimonian-Laird method. Heterogeneity was evaluated by I (2) statistic at a significance level of 50%. Publication bias was assessed by Egger's test.
RESULTS
Eleven articles including 2,074 breast cancer patients and 2,372 controls were summarized. Using the most common allele ε3 as a reference, the ε2 (OR =0.87, 95% CI =0.72-1.05, P=0.154, I (2)=0.0%) and ε4 (OR =1.07, 95% CI =0.80-1.42, P=0.654, I (2)=71.8%) alleles were not found to be significantly associated with breast cancer risk in the overall analyses. Subgroup analyses revealed that the comparison of allele ε4 with ε3 was significant in Asians (OR =1.58, 95% CI =1.17-6.32, P=0.003, I (2)=12.1%) and in studies that used the restriction fragment length polymorphism (RFLP) genotyping method (OR =1.27; 95% CI =1.01-1.61, P=0.045, I (2)=34.3%), and was marginally significant in hospital-based studies (OR =1.33; 95% CI =0.98-1.79, P=0.065, I (2)=30.2%), without heterogeneity. Moreover, the presence of the ε2 allele was significantly associated with breast cancer in small studies (total sample size <500) (OR =0.73, 95% CI =0.54-1.00, P=0.052, I (2)=0.0%) without heterogeneity. The Egger's test indicated low probabilities of publication bias.
CONCLUSION
We observed a significant association between APOE gene ε4 allele and breast cancer risk in Asian populations. Moreover, the findings of our subgroup analyses suggest that source of controls, genotyping platform, and sample size might be the potential causes of heterogeneity.
PubMed: 27022282
DOI: 10.2147/OTT.S94228 -
Cognitive and Behavioral Neurology :... Sep 2020Air pollution has a negative impact on one's health and on the central nervous system. We decided to assess studies that evaluated the relationship between air pollution...
Air pollution has a negative impact on one's health and on the central nervous system. We decided to assess studies that evaluated the relationship between air pollution and cognitive functions in children and adolescents by reviewing studies that had been published between January 2009 and May 2019. We searched three major databases for original works (26 studies) and for studies using brain imaging methods based on MRI (six studies). Adverse effects of air pollutants on selected cognitive or psychomotor functions were found in all of the studies. Exposure to nitrogen dioxide, for example, was linked to impaired working memory, general cognitive functions, and psychomotor functions; particulate matter 2.5 was linked to difficulties in working memory, short-term memory, attention, processing speed, and fine motor function; black carbon was linked to poor verbal intelligence, nonverbal intelligence, and working memory; airborne copper was linked to impaired attentiveness and fine motor skills; isophorone was linked to lower mathematical skills; and polycyclic aromatic hydrocarbons in fetal life were linked to lower intelligence scores. The studies using MRI showed that high concentrations of air pollutants were linked to changes in the brain's white matter or lower functional integration and segregation in children's brain networks. In view of the global increase in air pollution, there is a need for further research to elucidate the relationship between air pollution and cognitive and motor development in children. According to some studies, neuroinflammation, the e4 allele of the apolipoprotein E gene, and gutathione-S-transferase gene polymorphism processes may play a role.
Topics: Air Pollution; Child; Cognitive Dysfunction; Environmental Exposure; Female; Humans; Male; Particulate Matter
PubMed: 32889949
DOI: 10.1097/WNN.0000000000000235 -
Cardiovascular Therapeutics Oct 2016Warfarin is the most extensively used coumarin anticoagulant. It has been shown that the anticoagulant effect of warfarin is associated with genetic variation.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Warfarin is the most extensively used coumarin anticoagulant. It has been shown that the anticoagulant effect of warfarin is associated with genetic variation. Apolipoprotein E (ApoE) is a possible candidate to influence the maintenance dose of warfarin. ApoE affects the vitamin K cycle by mediating the uptake of vitamin K into the liver. The vitamin K cycle is the drug target of warfarin. However, the association between genetic variants of the APOE gene and warfarin dose requirement is still controversial.
METHODS
Revman 5.3 software was used to analyze the relationship between APOE genotypes and warfarin dose requirements.
RESULTS
In our meta-analysis, the E2/E2 genotype was significantly associated with warfarin dose. E2/E2 patients required 12% (P = 0.0002) lower mean daily warfarin dose than E3/E3 carriers. In addition, subgroup analysis showed that Asians with the E4/E4 genotype tended to need lower warfarin maintenance doses, while the African American E4/E4 carriers needed slightly higher doses than E3/E3 carriers; however, these subgroups were very small.
CONCLUSION
This is the first meta-analysis of the association between APOE genotypes and warfarin dose. APOE E2/E2 might be one of the factors affecting warfarin dose requirements. The effect of APOE may vary between ethnicities.
Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Apolipoproteins E; Blood Coagulation; Chi-Square Distribution; Drug Dosage Calculations; Ethnicity; Female; Gene Frequency; Genotype; Humans; International Normalized Ratio; Male; Middle Aged; Pharmacogenetics; Pharmacogenomic Variants; Phenotype; Polymorphism, Genetic; Warfarin
PubMed: 27062534
DOI: 10.1111/1755-5922.12186 -
Behavioural Brain Research Jan 2021This systematic review examined whether event-related potentials (ERPs) during higher cognitive processing can detect subtle, early signs of neurodegenerative disease....
This systematic review examined whether event-related potentials (ERPs) during higher cognitive processing can detect subtle, early signs of neurodegenerative disease. Original, empirical studies retrieved from PsycINFO and PubMed were reviewed if they analyzed patterns in cognitive ERPs (≥150 ms post-stimulus) differentiating mild cognitive impairment (MCI), Alzheimer's disease (AD), or cognitively intact elders who carry AD risk through the Apolipoprotein-E ε4 allele (ε4+) from healthy older adult controls (HC). The 100 studies meeting inclusion criteria (MCI = 47; AD = 47; ε4+ = 6) analyzed N200, P300, N400, and occasionally, later components. While there was variability across studies, patterns of reduced amplitude and delayed latency were apparent in pathological aging, consistent with AD-related brain atrophy and cognitive impairment. These effects were particularly evident in advanced disease progression (i.e., AD > MCI) and in later ERP components measured during complex tasks. Although ERP studies in intact ε4+ elders are thus far scarce, a similar pattern of delayed latency was notable, along with a contrasting pattern of increased amplitude, consistent with compensatory neural activation. This limited work suggests ERPs might be able to index early neural changes indicative of future cognitive decline in otherwise healthy elders. As ERPs are also accessible and affordable relative to other neuroimaging methods, their addition to cognitive assessment might substantively enhance early identification and characterization of neural dysfunction, allowing opportunity for earlier differential diagnosis and targeting of intervention. To evaluate this possibility there is urgent need for well-powered studies assessing late cognitive ERPs during complex tasks, particularly in healthy elders at risk for cognitive decline.
Topics: Alzheimer Disease; Cognitive Dysfunction; Evoked Potentials; Humans
PubMed: 32941881
DOI: 10.1016/j.bbr.2020.112904 -
Geriatrics & Gerontology International Feb 2021Heredity plays an important role in the pathogenesis of Alzheimer's disease (AD) especially for single-nucleotide polymorphism (SNPs) of susceptible genes, which is one... (Meta-Analysis)
Meta-Analysis
AIM
Heredity plays an important role in the pathogenesis of Alzheimer's disease (AD) especially for single-nucleotide polymorphism (SNPs) of susceptible genes, which is one of the significant factors in the pathogenesis of AD. The SNPs of BIN1 rs744373, BIN1 rs7561528 and GAB2 rs2373115 are associated with AD in Asian and white people.
METHODS
We included 34 studies with a total of 38 291 patients with AD and 55 538 controls of diverse races from four main databases. We used meta-analysis to obtain I -values and odds ratios of five genetic models in three SNPs. We carried out analysis of sensitivity, subgroup, publication bias and linkage disequilibrium test.
RESULTS
The forest plots showed the odds ratio value of the three SNPs was >1 in white individuals, but not Asian individuals, in their genetic model. The funnel plot was symmetrical, and the D'-value was 0.986 between rs744373 and rs7561528.
CONCLUSIONS
BIN1 rs744373, BIN1 rs7561528 and GAB2 rs2373115 are pathogenicity sites for AD in white people, and also rs7561528 belongs to a risk site in Asian people. The rs7561528 and rs744373 SNPs have strong linkage disequilibrium in Chinese people. In addition, apolipoprotein E ε4 status promotes them to result in the pathogenesis of AD. Geriatr Gerontol Int 2021; 21: 185-191.
Topics: Adaptor Proteins, Signal Transducing; Alzheimer Disease; Genetic Predisposition to Disease; Humans; Nuclear Proteins; Polymorphism, Single Nucleotide; Tumor Suppressor Proteins; White People
PubMed: 33331110
DOI: 10.1111/ggi.14109 -
Frontiers in Aging Neuroscience 2022Alzheimer's disease (AD) is a devastating neurodegenerative disorder with no cure, and available treatments are only able to postpone the progression of the disease....
BACKGROUND AND PURPOSE
Alzheimer's disease (AD) is a devastating neurodegenerative disorder with no cure, and available treatments are only able to postpone the progression of the disease. Mild cognitive impairment (MCI) is considered to be a transitional stage preceding AD. Therefore, prediction models for conversion from MCI to AD are desperately required. These will allow early treatment of patients with MCI before they develop AD. This study performed a systematic review and meta-analysis to summarize the reported risk prediction models and identify the most prevalent factors for conversion from MCI to AD.
METHODS
We systematically reviewed the studies from the databases of PubMed, CINAHL Plus, Web of Science, Embase, and Cochrane Library, which were searched through September 2021. Two reviewers independently identified eligible articles and extracted the data. We used the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies (CHARMS) checklist for the risk of bias assessment.
RESULTS
In total, 18 articles describing the prediction models for conversion from MCI to AD were identified. The dementia conversion rate of elderly patients with MCI ranged from 14.49 to 87%. Models in 12 studies were developed using the data from the Alzheimer's Disease Neuroimaging Initiative (ADNI). C-index/area under the receiver operating characteristic curve (AUC) of development models were 0.67-0.98, and the validation models were 0.62-0.96. MRI, apolipoprotein E genotype 4 (APOE4), older age, Mini-Mental State Examination (MMSE) score, and Alzheimer's Disease Assessment Scale cognitive (ADAS-cog) score were the most common and strongest predictors included in the models.
CONCLUSION
In this systematic review, many prediction models have been developed and have good predictive performance, but the lack of external validation of models limited the extensive application in the general population. In clinical practice, it is recommended that medical professionals adopt a comprehensive forecasting method rather than a single predictive factor to screen patients with a high risk of MCI. Future research should pay attention to the improvement, calibration, and validation of existing models while considering new variables, new methods, and differences in risk profiles across populations.
PubMed: 35493941
DOI: 10.3389/fnagi.2022.840386 -
Atherosclerosis Nov 2014Conflicting evidence exists on whether smoking acts as an effect modifier of the association between APOE genotype and risk of coronary heart disease (CHD). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Conflicting evidence exists on whether smoking acts as an effect modifier of the association between APOE genotype and risk of coronary heart disease (CHD).
METHODS AND RESULTS
We searched PubMed and EMBASE to June 11, 2013 for published studies reporting APOE genotype, smoking status and CHD events and added unpublished data from population cohorts. We tested for presence of effect modification by smoking status in the relationship between APOE genotype and risk of CHD using likelihood ratio test. In total 13 studies (including unpublished data from eight cohorts) with 10,134 CHD events in 130,004 individuals of European descent were identified. The odds ratio (OR) for CHD risk from APOE genotype (ε4 carriers versus non-carriers) was 1.06 (95% confidence interval (CI): 1.01, 1.12) and for smoking (present vs. past/never smokers) was OR 2.05 (95%CI: 1.95, 2.14). When the association between APOE genotype and CHD was stratified by smoking status, compared to non-ε4 carriers, ε4 carriers had an OR of 1.11 (95%CI: 1.02, 1.21) in 28,789 present smokers and an OR of 1.04 (95%CI 0.98, 1.10) in 101,215 previous/never smokers, with no evidence of effect modification (P-value for heterogeneity = 0.19). Analysis of pack years in individual participant data of >60,000 with adjustment for cardiovascular traits also failed to identify evidence of effect modification.
CONCLUSIONS
In the largest analysis to date, we identified no evidence for effect modification by smoking status in the association between APOE genotype and risk of CHD.
Topics: Adult; Aged; Alleles; Apolipoprotein E4; Cohort Studies; Coronary Disease; Female; Gene-Environment Interaction; Genotype; Heterozygote; Humans; Male; Middle Aged; Risk Factors; Smoking
PubMed: 25173947
DOI: 10.1016/j.atherosclerosis.2014.07.038 -
Journal of Alzheimer's Disease Reports 2023Alzheimer's disease (AD) has several risk factors. is the main one, and it has been suggested that there may be a synergy between it and as a risk factor.
Confirmed Synergy Between the ɛ4 Allele of Apolipoprotein E and the Variant K of Butyrylcholinesterase as a Risk Factor for Alzheimer's Disease: A Systematic Review and Meta-Analysis.
BACKGROUND
Alzheimer's disease (AD) has several risk factors. is the main one, and it has been suggested that there may be a synergy between it and as a risk factor.
OBJECTIVE
To investigate the association between and as a risk factor for AD.
METHODS
We searched PubMed, Web of Science, Embase, and Scopus on August 8, 2021 for studies that analyzed the association of and with AD. The random effect model was performed in meta-analysis according to age group. A chi-square was performed with the meta-analysis data to verify if the effect found is not associated only with the E4 allele.
RESULTS
Twenty-one studies with 6,853 subjects (3,528 AD and 3,325 Controls) were included in the meta-analysis. The quality of the evidence is moderate. There is a positive E4-K association for subjects with AD as shown by the odds ratio of 3.43. The chi-square meta test, which measures the probability that the E4-K association is due to chance, has an odds ratio of 6.155, indicating that the E4-K association is not a random event. The odds ratio of an E4-K association in subjects with AD increases to OR 4.46 for the 65- to 75-year-old group and OR 4.15 for subjects older than 75 years. The probability that the E4-K association is due to chance is ruled out by chi-square meta test values of OR 8.638 and OR 9.558.
CONCLUSION
The synergy between and is a risk factor for late-onset AD.
PubMed: 37483326
DOI: 10.3233/ADR-220084 -
Acta Neuropathologica Communications Jan 2022The initiation, anatomic pattern, and extent of tau spread in traumatic brain injury (TBI), and the mechanism by which TBI leads to long-term tau pathology, remain...
Association between single moderate to severe traumatic brain injury and long-term tauopathy in humans and preclinical animal models: a systematic narrative review of the literature.
BACKGROUND
The initiation, anatomic pattern, and extent of tau spread in traumatic brain injury (TBI), and the mechanism by which TBI leads to long-term tau pathology, remain controversial. Some studies suggest that moderate to severe TBI is sufficient to promote tau pathology; however, others suggest that it is simply a consequence of aging. We therefore conducted a systematic narrative review of the literature addressing whether a single moderate to severe head injury leads to long-term development of tauopathy in both humans and animal models.
METHODS
Studies considered for inclusion in this review assessed a single moderate to severe TBI, assessed tau pathology at long-term timepoints post-injury, comprised experimental or observational studies, and were peer-reviewed and published in English. Databases searched included: PUBMED, NCBI-PMC, EMBASE, Web of Science, Academic Search Premiere, and APA Psychnet. Search results were uploaded to Covidence®, duplicates were removed, and articles underwent an abstract and full-text screening process. Data were then extracted and articles assessed for risk of bias.
FINDINGS
Of 4,150 studies screened, 26 were eligible for inclusion, of which 17 were human studies, 8 were preclinical animal studies, and 1 included both human and preclinical animal studies. Most studies had low to moderate risk of bias. Most human and animal studies (n = 12 and 9, respectively) suggested that a single moderate to severe TBI resulted in greater development of long-term tauopathy compared to no history of head injury. This conclusion should be interpreted with caution, however, due to several limitations: small sample sizes; inconsistencies in controlling for confounding factors that may have affected tau pathology (e.g., family history of dementia or neurological illnesses, apolipoprotein E genotype, etc.), inclusion of mostly males, and variation in reporting injury parameters.
INTERPRETATION
Results indicate that a single moderate to severe TBI leads to greater chronic development of tauopathy compared to no history of head injury. This implies that tau pathology induced may not be transient, but can progressively develop over time in both humans and animal models. Targeting these tau changes for therapeutic intervention should be further explored to elucidate if disease progression can be reversed or mitigated.
Topics: Animals; Brain; Brain Injuries, Traumatic; Disease Models, Animal; Humans; Tauopathies
PubMed: 35101132
DOI: 10.1186/s40478-022-01311-0 -
Sleep Medicine Jan 2023The glymphatic system is thought to be responsible for waste clearance in the brain. As it is primarily active during sleep, different components of sleep, subjective... (Review)
Review
OBJECTIVE
The glymphatic system is thought to be responsible for waste clearance in the brain. As it is primarily active during sleep, different components of sleep, subjective sleep quality, and sleep patterns may contribute to glymphatic functioning. This systematic review aimed at exploring the effect of sleep components, sleep quality, and sleep patterns on outcomes associated with the glymphatic system in healthy adults.
METHODS
PubMed®, Scopus, and Web of Science were searched for studies published in English until December 2021. Articles subjectively or objectively investigating sleep components (total sleep time, time in bed, sleep efficiency, sleep onset latency, wake-up after sleep onset, sleep stage, awakenings), sleep quality, or sleep pattern in healthy individuals, on outcomes associated with glymphatic system (levels of amyloid-β, tau, α-synuclein; cerebrospinal fluid, perivascular spaces; apolipoprotein E) were selected.
RESULTS
Out of 8359 records screened, 51 studies were included. Overall, contradictory findings were observed according to different sleep assessment method. The most frequently assessed sleep parameters were total sleep time, sleep quality, and sleep efficiency. No association was found between sleep efficiency and amyloid-β, and between slow-wave activity and tau. Most of the studies did not find any correlation between total sleep time and amyloid-β nor tau level. Opposing results correlated sleep quality with amyloid-β and tau.
CONCLUSIONS
This review highlighted inconsistent results across the studies; as such, the specific association between the glymphatic system and sleep parameters in healthy adults remains poorly understood. Due to the heterogeneity of sleep assessment methods and the self-reported data representing the majority of the observations, future studies with universal study design and sleep methodology in healthy individuals are advocated.
Topics: Adult; Humans; Amyloid beta-Peptides; Brain; Glymphatic System; Sleep; Sleep Wake Disorders
PubMed: 36481512
DOI: 10.1016/j.sleep.2022.11.012