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Preventive Nutrition and Food Science Dec 2023Plant sterols/stanols are effective cholesterol-lowering agents. However, it is unclear whether the apolipoprotein E () genetic variants influence it. We investigated... (Review)
Review
Plant sterols/stanols are effective cholesterol-lowering agents. However, it is unclear whether the apolipoprotein E () genetic variants influence it. We investigated whether genetic variants modulate the responses of blood lipids to dietary intervention plant sterols/stanols in adults and if the intervention dose and duration, as well as the age and status of participants, influence this effect. Randomized clinical trials were identified by searching databases in the Cochrane Library. Random-effect models were used to estimate the pooled effect size of each outcome of interest total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein cholesterol, and triglycerides. Meta-regression and subgroup analysis were used to investigate the effects of potential modifiers on the outcomes of interest. Eleven articles were selected from 3,248 retrieved abstracts. Plant sterol/stanol intervention was associated with a more significant reduction in LDL levels in the E3 group [-0.251 mmol/L; 95% confidence interval (95% CI), -0.488 to -0.015] compared with both the E4 and E2 groups. In E4 carriers, the plant sterol/stanol intervention dose and duration resulted in a larger decrease in LDL levels (-0.088027 mmol/L; 95% CI, -0.154690 to -0.021364). In conclusion, genetic variants affected the response of blood LDL levels to supplementation with plant sterols/stanols, as individuals with E3 variant showed significantly decreased LDL levels compared with the other genotypes. However, future studies recruiting participants according to their genetic variants are needed to confirm our conclusion.
PubMed: 38188084
DOI: 10.3746/pnf.2023.28.4.377 -
Frontiers in Aging Neuroscience 2021Possession of one or two e4 alleles of the apolipoprotein E () gene is associated with cognitive decline and dementia risk. Some evidence suggests that physical activity...
INTRODUCTION
Possession of one or two e4 alleles of the apolipoprotein E () gene is associated with cognitive decline and dementia risk. Some evidence suggests that physical activity may benefit carriers of the e4 allele differently.
METHOD
We conducted a systematic review and meta-analysis of studies which assessed differences in the association between physical activity and: lipid profile, Alzheimer's disease pathology, brain structure and brain function in healthy adults. Searches were carried out in PubMed, SCOPUS, Web of Science and PsycInfo.
RESULTS
Thirty studies were included from 4,896 papers screened. Carriers of the e4 allele gained the same benefit from physical activity as non-carriers on most outcomes. For brain activation, e4 carriers appeared to gain a greater benefit from physical activity on task-related and resting-state activation and resting-state functional connectivity compared to non-carriers. analysis identified possible compensatory mechanisms allowing e4 carriers to maintain cognitive function.
DISCUSSION
Though there is evidence suggesting physical activity may benefit e4 carriers differently compared to non-carriers, this may vary by the specific brain health outcome, perhaps limited to brain activation. Further research is required to confirm these findings and elucidate the mechanisms.
PubMed: 35153725
DOI: 10.3389/fnagi.2021.815439 -
International Journal of Epidemiology Apr 2013At the APOE gene, encoding apolipoprotein E, genotypes of the ε2/ε3/ε4 alleles associated with higher LDL-cholesterol (LDL-C) levels are also associated with higher... (Meta-Analysis)
Meta-Analysis Review
Apolipoprotein E genotype, cardiovascular biomarkers and risk of stroke: systematic review and meta-analysis of 14,015 stroke cases and pooled analysis of primary biomarker data from up to 60,883 individuals.
BACKGROUND
At the APOE gene, encoding apolipoprotein E, genotypes of the ε2/ε3/ε4 alleles associated with higher LDL-cholesterol (LDL-C) levels are also associated with higher coronary risk. However, the association of APOE genotype with other cardiovascular biomarkers and risk of ischaemic stroke is less clear. We evaluated the association of APOE genotype with risk of ischaemic stroke and assessed whether the observed effect was consistent with the effects of APOE genotype on LDL-C or other lipids and biomarkers of cardiovascular risk.
METHODS
We conducted a systematic review of published and unpublished studies reporting on APOE genotype and ischaemic stroke. We pooled 41 studies (with a total of 9027 cases and 61,730 controls) using a Bayesian meta-analysis to calculate the odds ratios (ORs) for ischaemic stroke with APOE genotype. To better evaluate potential mechanisms for any observed effect, we also conducted a pooled analysis of primary data using 16 studies (up to 60,883 individuals) of European ancestry. We evaluated the association of APOE genotype with lipids, other circulating biomarkers of cardiovascular risk and carotid intima-media thickness (C-IMT).
RESULTS
The ORs for association of APOE genotypes with ischaemic stroke were: 1.09 (95% credible intervals (CrI): 0.84-1.43) for ε2/ε2; 0.85 (95% CrI: 0.78-0.92) for ε2/ε3; 1.05 (95% CrI: 0.89-1.24) for ε2/ε4; 1.05 (95% CrI: 0.99-1.12) for ε3/ε4; and 1.12 (95% CrI: 0.94-1.33) for ε4/ε4 using the ε3/ε3 genotype as the reference group. A regression analysis that investigated the effect of LDL-C (using APOE as the instrument) on ischaemic stroke showed a positive dose-response association with an OR of 1.33 (95% CrI: 1.17, 1.52) per 1 mmol/l increase in LDL-C. In the separate pooled analysis, APOE genotype was linearly and positively associated with levels of LDL-C (P-trend: 2 × 10(-152)), apolipoprotein B (P-trend: 8.7 × 10(-06)) and C-IMT (P-trend: 0.001), and negatively and linearly associated with apolipoprotein E (P-trend: 6 × 10(-26)) and HDL-C (P-trend: 1.6 × 10(-12)). Associations with lipoprotein(a), C-reactive protein and triglycerides were non-linear.
CONCLUSIONS
In people of European ancestry, APOE genotype showed a positive dose-response association with LDL-C, C-IMT and ischaemic stroke. However, the association of APOE ε2/ε2 genotype with ischaemic stroke requires further investigation. This cross-domain concordance supports a causal role of LDL-C on ischaemic stroke.
Topics: Apolipoproteins E; Biomarkers; Carotid Intima-Media Thickness; Cholesterol, LDL; Genetic Predisposition to Disease; Genotype; Humans; Lipids; Risk Factors; Stroke; Triglycerides
PubMed: 23569189
DOI: 10.1093/ije/dyt034 -
PloS One 2017Diets rich in flavonoids have been reported to have beneficial effects in the primary prevention of cardiovascular events. There are limited data, however, on the... (Meta-Analysis)
Meta-Analysis Review
Diets rich in flavonoids have been reported to have beneficial effects in the primary prevention of cardiovascular events. There are limited data, however, on the cardiovascular benefits of purified flavonoids. The aim of this systematic review and meta-analysis was to examine the reported effects of isolated flavonoids on aortic atherosclerosis in a mouse model. Medline, Pubmed, Science direct and Web of Science were searched to identify studies which examined the effect of isolated flavonoids on aortic atherosclerosis in apolipoprotein E deficient mice. A meta-analysis was performed to determine the overall effect of the flavonoids, and sub-analyses were performed to compare the effects of the flavonols and flavan-3-ols. Eleven studies, which examined a total of 208 mice receiving a flavonoid and 126 control mice, were included. Overall the flavonoids significantly reduced aortic atherosclerosis (SMD 1.10, 95% CI 0.69, 1.51). Of the 18 flavonoid interventions examined 12 were flavonols and 3 were flavan-3-ols. Sub-analyses suggested that the flavonols (SMD 1.31, 95% CI 0.66, 1.91) but not the flavan-3-ols (SMD 0.33, 95% CI -0.19, 0.85) significantly decreased atherosclerosis area. Of the eleven studies, only one examined histological markers of atherosclerosis plaque stability. Most studies did not report blinding of outcome assessors or reproducibility of the primary outcome, and did not justify the sample size used and flavonoid dose administered. Based on the included studies, the flavonols appear to be the most effective flavonoids for reducing aortic atherosclerotic lesion area in apolipoprotein E deficient mice.
Topics: Animals; Apolipoproteins E; Coronary Artery Disease; Flavonols; Humans; Mice
PubMed: 28742839
DOI: 10.1371/journal.pone.0181832 -
FEBS Open Bio 2015Published data regarding the association between Apolipoprotein E (ApoE) genetic variation and myocardial infarction (MI) risk were not always consistent. Therefore, the...
Published data regarding the association between Apolipoprotein E (ApoE) genetic variation and myocardial infarction (MI) risk were not always consistent. Therefore, the current meta-analysis was conducted to derive a more precise estimation of the association between ApoE polymorphism and MI risk. PubMed and Web of Science were searched to identify relevant studies. Summary odds ratio (ORs) and 95% confidence intervals (CIs) were calculated using random-effect or fixed-effect models based on the heterogeneity of included studies. All the tests were performed using Stata 11.0. A total of 22 eligible studies were identified in this meta-analysis. The results show that ApoE ε2 and ε4 alleles were associated with MI risk. The study suggests that there is close association between ApoE polymorphism and MI risk. It shows that ApoE ε2 allele is a protective factor of MI, while ε4 allele is a risk factor of MI, especially in Caucasian and Asian population. Nevertheless, well-designed, unbiased and larger sample size studies are required to confirm the results.
PubMed: 26636027
DOI: 10.1016/j.fob.2015.10.006 -
Biological & Pharmaceutical Bulletin 2018Although several studies have evaluated the efficacy of thiazolidinediones (TZD) for the treatment of Alzheimer's disease (AD), investigation of the impact of... (Meta-Analysis)
Meta-Analysis Review
Although several studies have evaluated the efficacy of thiazolidinediones (TZD) for the treatment of Alzheimer's disease (AD), investigation of the impact of apolipoprotein E (ApoE) gene polymorphisms on the efficacy of TZD remains insufficient. We investigated the impact by conducting a systematic review and meta-analysis. MEDLINE, Cochrane Library, and Japana Centra Revuo Medicina were searched to identify relevant studies based on eligibility criteria. Mean differences (MD) of Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) total score with 95% confidence intervals (CI) were calculated for subgroups stratified by ApoE genotype. To evaluate the impact of ApoE gene polymorphisms, meta-regression analysis was also conducted to calculate the regression coefficient (Coef) of ApoE expression status with 95% CI. Three randomized controlled studies comparing rosiglitazone and placebo, with a total of 2381 subjects met the eligibility criteria. ApoE expression status was reported in 983 individuals (ApoE4-positive, 141; ApoE4-negative, 842). When compared to placebo, rosiglitazone significantly decreased ADAS-Cog score in ApoE4-negative individuals (MD, -1.37; 95% CI, -2.09 to -0.65), but significantly increased ADAS-Cog score in ApoE4-positive individuals (MD, 2.18; 95% CI, 0.52 to 3.85). The meta-regression analysis showed a significant association between efficacy and ApoE expression status (Coef, 3.55; 95% CI, 1.42 to 5.68). Although the present results should be interpreted with caution because of the limited number of studies, our findings suggest that ApoE gene polymorphisms impact the efficacy of rosiglitazone for AD patients. This finding would provide useful information for the development of new agents for AD.
Topics: Alzheimer Disease; Apolipoproteins E; Humans; Neuroprotective Agents; PPAR gamma; Polymorphism, Genetic; Thiazolidinediones; Treatment Outcome
PubMed: 29962398
DOI: 10.1248/bpb.b17-00929 -
The Cochrane Database of Systematic... Jan 2016This is an update of a Cochrane review first published in 2001 and then updated in 2009. Vascular risk factors including high cholesterol levels increase the risk of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an update of a Cochrane review first published in 2001 and then updated in 2009. Vascular risk factors including high cholesterol levels increase the risk of dementia due to Alzheimer's disease and of vascular dementia. Some observational studies have suggested an association between statin use and lowered incidence of dementia.
OBJECTIVES
To evaluate the efficacy and safety of statins for the prevention of dementia in people at risk of dementia due to their age and to determine whether the efficacy and safety of statins for this purpose depends on cholesterol level, apolipoprotein E (ApoE) genotype or cognitive level.
SEARCH METHODS
We searched ALOIS (the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group), The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS, ClinicalTrials.gov and the World Health Organization (WHO) Portal on 11 November 2015.
SELECTION CRITERIA
We included double-blind, randomised, placebo-controlled trials in which statins were administered for at least 12 months to people at risk of dementia.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included two trials with 26,340 participants aged 40 to 82 years of whom 11,610 were aged 70 or older. All participants had a history of, or risk factors for, vascular disease. The studies used different statins (simvastatin and pravastatin). Mean follow-up was 3.2 years in one study and five years in one study. The risk of bias was low. Only one study reported on the incidence of dementia (20,536 participants, 31 cases in each group; odds ratio (OR) 1.00, 95% confidence interval (CI) 0.61 to 1.65, moderate quality evidence, downgraded due to imprecision). Both studies assessed cognitive function, but at different times using different scales, so we judged the results unsuitable for a meta-analysis. There were no differences between statin and placebo groups on five different cognitive tests (high quality evidence). Rates of treatment discontinuation due to non-fatal adverse events were less than 5% in both studies and there was no difference between statin and placebo groups in the risk of withdrawal due to adverse events (26,340 participants, 2 studies, OR 0.94, 95% CI 0.83 to 1.05).
AUTHORS' CONCLUSIONS
There is good evidence that statins given in late life to people at risk of vascular disease do not prevent cognitive decline or dementia. Biologically, it seems feasible that statins could prevent dementia due to their role in cholesterol reduction and initial evidence from observational studies was very promising. However, indication bias may have been a factor in these studies and the evidence from subsequent RCTs has been negative. There were limitations in the included studies involving the cognitive assessments used and the inclusion of participants at moderate to high vascular risk only.
Topics: Adult; Aged; Aged, 80 and over; Alzheimer Disease; Anticholesteremic Agents; Cognition; Dementia; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Middle Aged; Pravastatin; Randomized Controlled Trials as Topic; Simvastatin
PubMed: 26727124
DOI: 10.1002/14651858.CD003160.pub3 -
Disease Markers 2022Rising studies indicate that the apolipoprotein E (APOE) gene is related to the susceptibility of ischemic stroke (IS). However, certain consensus is limited by the lack... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Rising studies indicate that the apolipoprotein E (APOE) gene is related to the susceptibility of ischemic stroke (IS). However, certain consensus is limited by the lack of a large sample size of researches. This meta-analysis was performed to explore the potential association between the APOE gene and IS.
METHODS
To identify relevant case control studies in English publications by October 2020, we searched PubMed, Embase, Web of Science, and the Cochrane Library. Pooled odds ratios (ORs) with fixed- or random-effect models and corresponding 95% confidence intervals (CIs) were calculated to analyze potential associations.
RESULTS
A total of 55 researches from 32 countries containing 12207 IS cases and 27742 controls were included. The association between APOE gene 4 mutation and IS was confirmed (4 vs. 3 allele: pooled OR = 1.374, 95% CI, 1.214-1.556; 2/4 vs. 3/3: pooled OR = 1.233, 95% CI, 1.056-1.440; 3/4 vs. 3/3: pooled OR = 1.340, 95% CI, 1.165-1.542; 4/4 vs. 3/3: pooled OR = 1.833, 95% CI, 1.542-2.179; and APOE 4 carriers vs. non-4 carriers: pooled OR = 1.377; 95% CI, 1.203-1.576). Interestingly, APOE 4 mutation showed a dose-response correlation with IS risk (4/4 vs. 2/4: pooled OR = 1.625; 95% CI, 1.281-2.060; 4/4 vs. 3/4: pooled OR = 1.301; 95% CI, 1.077-1.571). Similar conclusions were drawn in the small artery disease (SAD) subtype, but not in large artery atherosclerosis (LAA) or in cardioaortic embolism (CE), by subgroup analysis.
CONCLUSIONS
These observations reveal that specific APOE 4 mutation was significantly associated with the risk of IS in a dose-dependent manner, while APOE 4 mutation was related to SAD subtype onset without a cumulative effect.
Topics: Apolipoprotein E4; Humans; Ischemic Stroke; Polymorphism, Genetic; Risk Factors
PubMed: 35154509
DOI: 10.1155/2022/1407183 -
Dementia and Geriatric Cognitive... 2011The ε4 allele of apolipoprotein E (APOE) is associated with Alzheimer's disease (AD). However, attributable risk due to APOE4 varies by region and by race/ethnicity. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The ε4 allele of apolipoprotein E (APOE) is associated with Alzheimer's disease (AD). However, attributable risk due to APOE4 varies by region and by race/ethnicity.
METHODS
A literature review and meta-analysis were conducted to estimate the prevalence of APOE4 by geographic area among AD patients.
RESULTS
Although estimates varied significantly by study design and case definition, AD patients recruited in Asian and southern European/Mediterranean communities seemed to have significantly lower E4 carrier status estimates (37 and 43%) than those recruited in North America (58%) or northern Europe (64%; all: p < 0.05).
CONCLUSIONS
APOE4 genotype frequency varies among AD patients in regional patterns similar to that of the general population. Study level differences may also contribute to the heterogeneity of published estimates of APOE4 in AD cases.
Topics: Alleles; Alzheimer Disease; Apolipoprotein E4; Autopsy; Data Interpretation, Statistical; Environment; Gene Frequency; Genetic Predisposition to Disease; Geography; Heterozygote; Humans; Regression Analysis; Tissue Banks
PubMed: 21124030
DOI: 10.1159/000321984