Association between Apolipoprotein E polymorphism and myocardial infarction risk: A systematic review and meta‐analysis

Wang, Yi-Lian; Sun, Lixian; Zhang, Li; Hui, Xu; Zheng, Dong; Wang, Luoqing; Wang, Minglang

doi:10.1016/j.fob.2015.10.006

Cited by 18 publications

(21 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Xu et al found similar results which showed that the ε4 allele had a 46% higher risk of CAD (OR = 1.46, 95% CI = 1.28–1.66) (Xu et al, 2016 ). Similar findings were also observed in other meta-analysis (Yin et al, 2013 ; Xu et al, 2014 , 2016 ; Zhang et al, 2014a , 2015 ; Wang et al, 2015b ). Interestingly, the role of APOE -ε2 allele in the risk of CAD may be dependent on the patient ethnicity (Xu et al, 2016 ).…”

Section: Discussionsupporting

confidence: 89%

The Associations between Apolipoprotein E Gene Epsilon2/Epsilon3/Epsilon4 Polymorphisms and the Risk of Coronary Artery Disease in Patients with Type 2 Diabetes Mellitus

et al. 2017

View full text Add to dashboard Cite

Background and Objective: Apolipoprotein E (APOE) plays important roles in lipoprotein metabolism and cardiovascular disease. Evidence suggests the APOE gene epsilon2/epsilon3/epsilon4 (ε2/ε3/ε4) polymorphisms might be associated with the susceptibility of coronary artery disease (CAD) in patients with type 2 diabetes mellitus (T2DM). However, no clear consensus has yet been established. Therefore, the aim of this meta-analysis is to provide a precise conclusion on the potential association between APOE ε2/ε3/ε4 polymorphisms and the risk of CAD in patients with T2DM based on case-control studies.Methods: Pubmed, Embase, Chinese National Knowledge Infrastructure (CNKI), and Wanfang databases were searched for all relevant studies prior to August 2017 in English and Chinese language. The pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were used to assess the strength of the relationships. The between-study heterogeneity was evaluated by Cochran's Q-test and the I2 index to adopt fixed- or random- effect models.Results: A total of 13 studies were eligible for inclusion. There was evidence for significant associations between APOE ε4 mutation and the risk of CAD in patients with T2DM (for ε3/ε4 vs. ε3/ε3: OR = 1.69, 95% CI = 1.38–2.08, P < 0.001; for ε4/ε4 vs. ε3/ε3: OR = 2.72, 95% CI = 1.61–4.60, P < 0.001; for ε4/ε4+ε3/ε4 vs. ε3/ε3: OR = 1.83, 95% CI = 1.52–2.22, P < 0.001; for ε4 allele vs. ε3 allele: OR = 1.64, 95% CI = 1.40–1.94, P < 0.001). In contrast, no significant associations were found in genetic model of APOE ε2 mutation (for ε2/ε2 vs. ε3/ε3: OR = 1.67, 95% CI = 0.90–3.09, P = 0.104; for ε2/ε3 vs. ε3/ε3: OR = 1.18, 95% CI = 0.93–1.51, P = 0.175; for ε2/ε2+ε2/ε3 vs. ε3/ε3: OR = 1.26, 95% CI = 0.88–1.82, P = 0.212; for ε2 allele vs. ε3 allele: OR = 1.34, 95% CI = 0.98–1.84, P = 0.07).Conclusions: The APOE gene ε4 mutation is associated with an increased risk of CAD in patients with T2DM, while the ε2 variation has null association with this disease.

show abstract

Section: Discussionsupporting

confidence: 89%

The Associations between Apolipoprotein E Gene Epsilon2/Epsilon3/Epsilon4 Polymorphisms and the Risk of Coronary Artery Disease in Patients with Type 2 Diabetes Mellitus

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Levels of plasma APOE and, generally also, high-density lipoprotein cholesterol (HDL-C) decrease in a perfect parametric fashion across the six APOE genotypes (2/2 > 2/3 > 2/4 > 3/3 > 3/4 > 4/4; Figure 4A), and the reverse is true for levels of low-density lipoprotein cholesterol (LDL-C; Figure 4B) (Bennet et al, 2007;Khan et al, 2013;Rasmussen, 2016). A similar stepwise pattern is seen in the risk for coronary artery disease (CAD) and myocardial infarction (MI), where APOE2 carriers have the least risk, APOE4 carriers have the greatest risk, and APOE3 carriers fall in the middle (Anand et al, 2009;Bennet et al, 2007;Wang et al, 2015;Xu et al, 2016; Figure 4E). For comparison, the risk for AD across genotypes is shown in Figure 4D.…”

Section: Cardiovascular Diseasementioning

confidence: 80%

“…Importantly, they also (A-E) Across all six combination of APOE alleles, clear parametric decreases can be observed for plasma APOE levels (A) and increases for low density lipoprotein cholesterol (LDL-C) levels [mean ± SEM] (B), while TG levels are marked by a U-shape (geometric mean ± SEM) (C), indicating risk for hypertriglyceridemia in APOE2 and APOE4 carriers (Rasmussen, 2016). The parametric association of APOE genotypes with lipid traits is also reflected in the association with risk, indicated by OR ± SE, for AD (pathologically confirmed, Caucasian subset; Farrer et al, 1997) (D) and myocardial infarction (MI) (Wang et al, 2015) (E). (F) While the APOE-related risk for AD follows APOE2 > APOE3 > APOE4, cerebral amyloid angiopathy (CAA) and related risk for intracerebral lobar hemorrhage display a U-shape (% probability of cases versus controls; median ± minmax), indicating increased risk for both APOE2 and APOE4 carriers (Biffi et al, 2010).…”

Section: Other Neurodegenerative Disordersmentioning

confidence: 99%

A Quarter Century of APOE and Alzheimer’s Disease: Progress to Date and the Path Forward

Belloy

Napolioni

Greicius

2019

Neuron

404

354

View full text Add to dashboard Cite

Alzheimer's disease (AD) is considered a polygenic disorder. This view is clouded, however, by lingering uncertainty over how to treat the quasi ''monogenic'' role of apolipoprotein E (APOE). The APOE4 allele is not only the strongest genetic risk factor for AD, it also affects risk for cardiovascular disease, stroke, and other neurodegenerative disorders. This review, based mostly on data from human studies, ranges across a variety of APOE-related pathologies, touching on evolutionary genetics and risk mitigation by ethnicity and sex. The authors also address one of the most fundamental question pertaining to APOE4 and AD: does APOE4 increase AD risk via a loss or gain of function? The answer will be of the utmost importance in guiding future research in AD. (A) The three main APOE isoforms APOE2, APOE3, and APOE4, respectively, encoded by the Apolipoprotein E2, E3, and E4 alleles, are the result of non-synonymous polymorphisms that cause amino acid changes at position 112 and 158 of the APOE protein (Rall et al., 1982; Weisgraber et al., 1981). APOE3 is the most common variant in the general population. The APOE4 variant is a major genetic risk factor for AD, while APOE2 is protective (Farrer et al., 1997). (B) Structural models of lipid-free APOE are shown for each major isoform, based on X-ray crystallography, structure prediction, and circular dichroism spectroscopy (Zhong and Weisgraber, 2009). The N-terminal domain contains APOE's low-density lipoprotein receptor (LDLR) region at amino acid residues 134-150, while the C-terminal holds the lipid-binding region at residues 244-272. Amino acid substitutions in APOE4 promote a salt bridge between Arg61 and Glu255, which, compared to the APOE2 and APOE3 variants, drives increased domain interaction between the N-and C-terminal domains. In (A), APOE allele frequencies are obtained, with permission, from American

show abstract

“…The other studied apolipoprotein ApoE is found in chylomicrons and intermediate density lipoprotein (IDL) that is essential for the normal catabolism of triglyceride-rich lipoprotein constituents and cholesterol metabolism [121]. The ApoE gene, mapped on chromosome 19q13.32 in a cluster with ApoC1 and ApoC 2, is highly polymorphic [122], with 3 major alleles according to the amino acids at positions 130 (rs429358; c.388 T > C) and 176 (rs7412; c.526C > T) in exon 4: ApoE 2 (cys130/cys176), ApoE 3 (cys130/arg176), and ApoE 4 (arg130/arg176) (ensemble.org).…”

Section: Discussionmentioning

confidence: 99%

“…The ApoE gene, mapped on chromosome 19q13.32 in a cluster with ApoC1 and ApoC 2, is highly polymorphic [122], with 3 major alleles according to the amino acids at positions 130 (rs429358; c.388 T > C) and 176 (rs7412; c.526C > T) in exon 4: ApoE 2 (cys130/cys176), ApoE 3 (cys130/arg176), and ApoE 4 (arg130/arg176) (ensemble.org). The ApoE polymorphisms were found to affect mRNA transcription and result in increased plasma cholesterol and triglyceride with impaired clearance of lipids from the bloodstream [121]. Moreover, knockout mice lacking ApoE developed extreme hypercholesterolemia after a high-fat diet [123].…”

Section: Discussionmentioning

confidence: 99%

Atherosclerotic and thrombotic genetic and environmental determinants in Egyptian coronary artery disease patients: a pilot study

Fawzy

Toraih

Aly

et al. 2017

BMC Cardiovasc Disord

View full text Add to dashboard Cite

BackgroundCoronary artery disease (CAD) is the leading cause of morbidity and mortality worldwide. Multiple genetic variants in combination with various environmental risk factors have been implicated. This study aimed to investigate the association of twelve thrombotic and atherosclerotic gene variants in combination with other environmental risk factors with CAD risk in a preliminary sample of Egyptian CAD patients.MethodsTwenty three consecutive CAD patients undergoing diagnostic coronary angiography and 34 unrelated controls, have been enrolled in the study. Genotyping was based on polymerase chain reaction and reverse multiplex hybridization. Five genetic association models were tested. Data distribution and variance homogeneity have been checked by Shapiro-Wilk test and Levene test, respectively; then the appropriate comparison test was applied. Spearman’s rank correlation coefficient was used for correlation analysis and logistic regression has been performed to adjust for significant risk factors. Clustering the study participants according to gene-gene and gene-environment interaction has been done by Detrended Correspondence Analysis (DCA).ResultsThe univariate analysis indicated that the five variants; rs1800595 (FVR2; factor 5), rs1801133 (MTHFR; 5,10-methylenetetrahydrofolate reductase), rs5918 (HPA-1; human platelet antigen 1), rs1799752 (ACE; angiotensin-converting enzyme), and rs7412 and rs429358 (ApoE; apolipoprotein E) were significantly associated with CAD susceptibility under different genetic models. Multivariate analysis revealed clustering of the study population into three patient groups (P) and one control group. FVR2 was the most variant associated with CAD patients, combined with the factor V Leiden (FVL) variant in P1 cluster and with both ACE and MTHFR 667C > T in P2. Whereas, P3 was mostly affected by both MTHFR 667C > T and FXIII (factor 13) V89L mutations. When combined with traditional risk factors, P1 was mostly affected by dyslipidemia, smoking and hypertension, while P2 was mostly affected by their fasting blood sugar levels and ApoE variant.ConclusionsTaken together, these preliminary results could have predictive value to be applied in refining a risk profile for our CAD patients, in order to implement early preventive interventions including specific antithrombotic therapy. Further large scale and follow-up studies are highly recommended to confirm the study findings.Electronic supplementary materialThe online version of this article (doi:10.1186/s12872-016-0456-3) contains supplementary material, which is available to authorized users.

show abstract

Association between Apolipoprotein E polymorphism and myocardial infarction risk: A systematic review and meta‐analysis

Abstract: HighlightsThis study suggests that there is close association between ApoE polymorphism and MI risk.ApoE ε2 allele is a protective factor of MI.ε4 allele is a risk factor for MI, especially in Caucasian and Asian populations.

Cited by 18 publications

References 37 publications

The Associations between Apolipoprotein E Gene Epsilon2/Epsilon3/Epsilon4 Polymorphisms and the Risk of Coronary Artery Disease in Patients with Type 2 Diabetes Mellitus

The Associations between Apolipoprotein E Gene Epsilon2/Epsilon3/Epsilon4 Polymorphisms and the Risk of Coronary Artery Disease in Patients with Type 2 Diabetes Mellitus

A Quarter Century of APOE and Alzheimer’s Disease: Progress to Date and the Path Forward

Atherosclerotic and thrombotic genetic and environmental determinants in Egyptian coronary artery disease patients: a pilot study

Contact Info

Product

Resources

About