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Meta-analysis of the association between Apolipoprotein E polymorphism and risks of myocardial infarction.
Shao, A, Shi, J, Liang, Z, Pan, L, Zhu, W, Liu, S, Xu, J, Guo, Y, Cheng, Y, Qiao, Y
BMC cardiovascular disorders. 2022;(1):126
Abstract
BACKGROUND Myocardial infarction (MI) remains the leading cause of death and disability among cardiovascular diseases worldwide. Studies show that elevated low-density lipid protein cholesterol (LDL-C) levels confer the highest absolute risk of MI, and Apolipoprotein E (ApoE) is implicated in regulating levels of triglycerides (TGs), cholesterol, and LDL-C. Our study aimed to evaluate the association between APOE polymorphism and MI, and to provide evidence for the etiology of MI. METHODS Case-control studies on the association between APOE polymorphisms and the risk of myocardial infarction were included by searching PubMed, Web of Science, and CNKI, and this meta-analysis was written in accordance with PRISMA guideline statement. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using either random-effects or fixed-effects models by R software. RESULTS A total of 33 eligible articles involving 13,706 cases and 14,817 controls were finally selected. The pooled analysis based on the total eligible articles showed that the risk of MI was associated with ApoE epsilon 2 and epsilon 4 alleles. The results showed that patients with MI had a low frequency of the ε2 allele (OR 0.74, 95% CI 0.64-0.86) and a high frequency of the ε4 allele (OR 1.24, 95% CI 1.09-1.42). CONCLUSIONS APOE ε2-involved genotypes may be protective factors for MI; in contrast, ε4-involved genotypes (ε4/ε3 vs. ε3/ε3, and ε4/ε4 vs. ε3/ε3) may be risk factors for MI.
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Association of Apolipoprotein E gene polymorphism with Preeclampsia: a meta-analysis.
Abyadeh, M, Heydarinejad, F, Khakpash, M, Asefi, Y, Shab-Bidar, S
Hypertension in pregnancy. 2020;(2):196-202
Abstract
Objective: The aim of this meta-analysis was to examine the association of ApoE polymorphism with the risk of developing PE.Methods: A comprehensive search was carried out through PubMed, Scopus, and Embase. The ORs with corresponding 95% CIs were extracted. Fixed model was used for meta-analysis and in case of existing heterogeneity a random-effects model was applied.Results: Association of ApoE polymorphism with the risk of developing PE was not statistically significant (OR = 0.86, 95% CI: 0.67-1.11; OR = 0.92, 95%CI: 0.73-1.15, respectively for ε2 and ε4).Conclusion: ApoE polymorphism might not be associated with the risk of PE.
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Association between Apolipoprotein E Gene Polymorphism and Alzheimer's Disease in an Iranian Population: A Meta-Analysis.
Abyadeh, M, Djafarian, K, Heydarinejad, F, Alizadeh, S, Shab-Bidar, S
Journal of molecular neuroscience : MN. 2019;(4):557-562
Abstract
The development of Alzheimer's disease (AD) has been strongly linked to the apolipoprotein E (APOE) polymorphism. A number studies have reported that the APOE ε4 allele is a genetic risk factor for developing AD, whereas the APOE ε2 and APOE ε3 alleles are considered to be neutral or even protective; however, there are conflicting data about these relationships in certain ethnic populations. Several meta-analyses have been performed to reduce the heterogeneity of results from different studies and estimate the real association in specific ethnicities. The aim of this study was to investigate the association between the APOE polymorphism and AD in an Iranian population. Our results showed a higher incidence of AD among individuals carrying the APOE ε4 allele (OR = 4.81, 95% CI: 3.28-7.05), more notably in those with the APOE ε4/e4 genotype (OR = 7.47, 95% CI: 2.35-23.73), while carrying the APOE ε3 allele was demonstrated to have a protective effect (OR = 0.40, 95% CI: 0.30-0.54). The association between the APOE ε2 allele and AD was not statically significant. However, further studies focusing on other parameters such as age, sex and environmental conditions are needed to reveal the true association between the APOE polymorphism and AD.
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The association between the SLCO1B1, apolipoprotein E, and CYP2C9 genes and lipid response to fluvastatin: a meta-analysis.
Xiang, Q, Zhang, X, Ma, L, Hu, K, Zhang, Z, Mu, G, Xie, Q, Chen, S, Cui, Y
Pharmacogenetics and genomics. 2018;(12):261-267
Abstract
OBJECTIVE The aim of this study was to determine the impact of the SLCO1B1, apolipoprotein E (ApoE), and CYP2C9 genotypes on the lipid-lowering efficacy of fluvastatin. METHODS We performed electronic searches on the PubMed, Embase, and Cochrane Library databases to identify studies published through October 2017. Studies that reported the effect estimates with 95% confidence intervals (CIs) of total cholesterol (TC), triglyceride, low-density lipoprotein (LDL), and high-density lipoprotein were included so that the different genotype categories could be compared. Weighted mean difference (WMD) was used to summarize the effect estimates. RESULTS Six studies, involving a total of 1171 individuals, were included in the final analysis. We noted that the patient carrier SLCO1B1 521TT was associated with greater change in TC (WMD: -2.98; 95% CI: -5.12 to -0.84; P=0.006) and LDL (WMD: -5.58; 95% CI: -10.64 to -0.52; P=0.031) compared with 521TC or CC. Furthermore, the patient carrier ApoE*2/*3 showed more change in high-density lipoprotein compared with ApoE*3/*3 (WMD: 18.76; 95% CI: 8.97-28.55; P<0.001) and ApoE*3/*4 or *4/*4 (WMD: 22.51; 95% CI: 0.98-44.04; P=0.040). Finally, the CYP2C9 genotypes showed no correlation with the effects of fluvastatin on TC, triglyceride, and LDL. CONCLUSION The findings of this study suggested that the SLCO1B1 and ApoE polymorphisms could influence the lipid-lowering effect of fluvastatin, whereas the CYP2C9 genotypes were not associated with the therapeutic effects of fluvastatin.
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Age-related cognitive decline and associations with sex, education and apolipoprotein E genotype across ethnocultural groups and geographic regions: a collaborative cohort study.
Lipnicki, DM, Crawford, JD, Dutta, R, Thalamuthu, A, Kochan, NA, Andrews, G, Lima-Costa, MF, Castro-Costa, E, Brayne, C, Matthews, FE, et al
PLoS medicine. 2017;(3):e1002261
Abstract
BACKGROUND The prevalence of dementia varies around the world, potentially contributed to by international differences in rates of age-related cognitive decline. Our primary goal was to investigate how rates of age-related decline in cognitive test performance varied among international cohort studies of cognitive aging. We also determined the extent to which sex, educational attainment, and apolipoprotein E ε4 allele (APOE*4) carrier status were associated with decline. METHODS AND FINDINGS We harmonized longitudinal data for 14 cohorts from 12 countries (Australia, Brazil, France, Greece, Hong Kong, Italy, Japan, Singapore, Spain, South Korea, United Kingdom, United States), for a total of 42,170 individuals aged 54-105 y (42% male), including 3.3% with dementia at baseline. The studies began between 1989 and 2011, with all but three ongoing, and each had 2-16 assessment waves (median = 3) and a follow-up duration of 2-15 y. We analyzed standardized Mini-Mental State Examination (MMSE) and memory, processing speed, language, and executive functioning test scores using linear mixed models, adjusted for sex and education, and meta-analytic techniques. Performance on all cognitive measures declined with age, with the most rapid rate of change pooled across cohorts a moderate -0.26 standard deviations per decade (SD/decade) (95% confidence interval [CI] [-0.35, -0.16], p < 0.001) for processing speed. Rates of decline accelerated slightly with age, with executive functioning showing the largest additional rate of decline with every further decade of age (-0.07 SD/decade, 95% CI [-0.10, -0.03], p = 0.002). There was a considerable degree of heterogeneity in the associations across cohorts, including a slightly faster decline (p = 0.021) on the MMSE for Asians (-0.20 SD/decade, 95% CI [-0.28, -0.12], p < 0.001) than for whites (-0.09 SD/decade, 95% CI [-0.16, -0.02], p = 0.009). Males declined on the MMSE at a slightly slower rate than females (difference = 0.023 SD/decade, 95% CI [0.011, 0.035], p < 0.001), and every additional year of education was associated with a rate of decline slightly slower for the MMSE (0.004 SD/decade less, 95% CI [0.002, 0.006], p = 0.001), but slightly faster for language (-0.007 SD/decade more, 95% CI [-0.011, -0.003], p = 0.001). APOE*4 carriers declined slightly more rapidly than non-carriers on most cognitive measures, with processing speed showing the greatest difference (-0.08 SD/decade, 95% CI [-0.15, -0.01], p = 0.019). The same overall pattern of results was found when analyses were repeated with baseline dementia cases excluded. We used only one test to represent cognitive domains, and though a prototypical one, we nevertheless urge caution in generalizing the results to domains rather than viewing them as test-specific associations. This study lacked cohorts from Africa, India, and mainland China. CONCLUSIONS Cognitive performance declined with age, and more rapidly with increasing age, across samples from diverse ethnocultural groups and geographical regions. Associations varied across cohorts, suggesting that different rates of cognitive decline might contribute to the global variation in dementia prevalence. However, the many similarities and consistent associations with education and APOE genotype indicate a need to explore how international differences in associations with other risk factors such as genetics, cardiovascular health, and lifestyle are involved. Future studies should attempt to use multiple tests for each cognitive domain and feature populations from ethnocultural groups and geographical regions for which we lacked data.
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Influence of APOE Gene Polymorphism on Interindividual and Interethnic Warfarin Dosage Requirement: A Systematic Review and Meta-Analysis.
Yu, WY, Sun, X, Wadelius, M, Huang, L, Peng, C, Ma, WL, Yang, GP
Cardiovascular therapeutics. 2016;(5):297-307
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Abstract
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.
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Significant interaction of APOE rs4420638 polymorphism with HDL-C and APOA-I levels in coronary heart disease in Han Chinese men.
Huang, Y, Ye, HD, Gao, X, Nie, S, Hong, QX, Ji, HH, Sun, J, Zhou, SJ, Fei, B, Li, KQ, et al
Genetics and molecular research : GMR. 2015;(4):13414-24
Abstract
Apolipoprotein E (APOE) is recognized for its importance in lipoprotein metabolism and cardiovascular disease. We evaluated the association between APOE rs4420638 genotypes and circulating lipid concentrations along with the risk of coronary heart disease (CHD). We conducted a case-control study involving 1508 individuals to investigate the contribution of rs4420638 to the risk of CHD in Han Chinese. In addition, we performed a meta-analysis to evaluate the association between rs4420638 and CHD in Europeans and Asians. The results show that rs4420638 is significantly correlated with increased CHD risk in male Han Chinese [P = 0.040, odds ratio (OR) = 1.34, 95% confidential interval (95%CI) = 1.01-1.78] and is likely to increase the risk of CHD under the dominant model in males (P = 0.036, OR = 1.38, 95%CI = 1.02-1.88). A further subgroup analysis by rs4420638 genotype found a significant association of rs4420638 AA with high-density lipoprotein cholesterol (HDL-C) (P = 0.012) and APOA-I levels (P = 0.0001) in males. The meta-analysis suggests that rs4420638 significantly increases the risk of CHD (OR = 1.18, 95%CI = 1.14-1.22, P < 0.0001, fixed-effect method). Our case-control study shows that rs4420638 genotype AA has a significant association with the concentrations of circulating HDL-C and APOA-I in CHD in Han Chinese males. The meta-analysis suggests that rs4420638 is associated with CHD risk in Europeans and Asians.
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PPARγ Pro12Ala and His447His polymorphisms and susceptibility to Alzheimer's disease: a meta-analysis.
Lee, YH, Song, GG
Genetics and molecular research : GMR. 2015;(2):7248-57
Abstract
We investigated whether Pro12Ala (C→G) and His447His (C→T) polymorphisms of the peroxisome proliferator-activated receptor gamma (PPARγ) gene are associated with susceptibility to Alzheimer's disease (AD). We conducted a meta-analysis of the associations between the PPARγ Pro12Ala and His447His polymorphisms and AD in subjects. The meta-analysis was performed according to the apolipoprotein E (APOE) ɛ4 allele status. A total of eight studies were considered in our meta-analysis, comprising 2948 patients with AD and 3753 controls. Meta-analysis showed no association between AD and the PPARγ Pro12Ala G allele in any of the study subjects [odds ratio (OR) = 1.013, 95% confidence interval (95%CI) = 0.906-1.132, P = 0.821] or in the European and Asian populations (OR = 0.997, 95%CI = 0.890-1.118, P = 0.965; OR = 1.409, 95%CI = 0.832-2.387, P = 0.202, respectively). We tested whether the APOE ɛ4 allele affects the association between the PPARγ Pro12Ala polymorphism and AD. Meta-analysis showed no association between AD and the PPARγ G allele in any of the study subjects with or without the APOE ɛ4 allele. Meta-analysis showed no association between AD and the PPARγ His447His T allele in the European population (OR for T allele = 0.912, 95%CI = 0.732-1.136, P = 0.409). This meta-analysis has shown that there is a lack of association between the PPARγ Pro12Ala and His447His polymorphisms and AD risk.
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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.
Khan, TA, Shah, T, Prieto, D, Zhang, W, Price, J, Fowkes, GR, Cooper, J, Talmud, PJ, Humphries, SE, Sundstrom, J, et al
International journal of epidemiology. 2013;(2):475-92
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Abstract
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.
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Associations of APOE gene polymorphisms with bone mineral density and fracture risk: a meta-analysis.
Peter, I, Crosier, MD, Yoshida, M, Booth, SL, Cupples, LA, Dawson-Hughes, B, Karasik, D, Kiel, DP, Ordovas, JM, Trikalinos, TA
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2011;(4):1199-209
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Abstract
UNLABELLED To determine the association of the Apolipoprotein E (APOE) E4 gene polymorphism with bone mineral density (BMD) and fractures we conducted a meta-analysis of 17 reports. Despite lower trochanteric and lumbar BMD in APOE4 carriers, there is insufficient evidence to support a consistent association of APOE with bone health. INTRODUCTION APOE has been studied for its potential role in osteoporosis risk. It is hypothesized that genetic variation at APOE locus, known as E2, E3, and E4, may modulate BMD through its effects on lipoproteins and vitamin K transport. The purpose of this study was to determine the association of the APOE-E4 gene polymorphism with bone-related phenotypes. METHODS We conducted a meta-analysis that combined newly analyzed individual data from two community-based cohorts, the Framingham Offspring Study (N = 1,495) and the vitamin K clinical trial (N = 377), with 15 other eligible published reports. Bone phenotypes included BMD measurements of the hip (total hip and trochanteric and femoral neck sites) and lumbar spine (from the L2 to L4 vertebrae) and prevalence or incidence of vertebral, hip, and other fractures. RESULTS In sex-pooled analyses, APOE4 carriers had a 0.018 g/cm(2) lower weighted mean trochanteric BMD than non carriers (p = 0.0002) with no evidence for between-study heterogeneity. A significant association was also detected with lumbar spine BMD (p = 0.006); however, inter-study heterogeneity was observed. Associations with lumbar spine and trochanteric BMD were observed predominantly in women and became less significant in meta-regression (p = 0.055 and 0.01, respectively). There were no consistent associations of APOE4 genotype with BMD at other skeletal sites or with fracture risk. CONCLUSIONS Based on these findings, there is insufficient evidence to support a strong and consistent association of the APOE genotype with BMD and fracture incidence.