Apolipoprotein E and Dementia in Parkinson Disease

Department of Neurology, University of North Carolina School of Medicine, Chapel Hill 27599-7025, USA.
JAMA Neurology (Impact Factor: 7.42). 03/2006; 63(2):189-93. DOI: 10.1001/archneur.63.2.189
Source: PubMed


To understand the relationship of apolipoprotein E (APOE) polymorphism to dementia in Parkinson disease (PD) because the APOE epsilon4 allele is linked to Alzheimer disease.
We reviewed MEDLINE, BIOSIS Previews, and ISI Web of Science from January 1, 1966, to May 7, 2004, supplemented by citation analysis from retrieved articles.
Case-control studies using clinical or pathologic criteria for PD and dementia, and with complete APOE genotype frequencies data.
We compared estimated prevalence odds ratios for dementia in PD in relation to each allele. We also looked for evidence of heterogeneity and publication bias and performed a stratified analysis on several study characteristics.
Data analyses suggest publication bias and heterogeneity of source data for the epsilon4 allele (homogeneity P = .2; Begg and Mazumdar, P = .06; and Egger et al, P = .1). The estimated odds ratios for development of dementia in PD are 1.6 for epsilon4 (95% confidence interval, 1.0-2.5); 1.3 for epsilon2 (95% confidence interval, 0.73-2.4); and 0.54 for epsilon3 (95% confidence interval, 0.18-1.6). The odds ratio estimates for epsilon4 were higher for studies published in 1996 or later (2.3 vs 1.0) and for studies conducted outside North American sites (2.4 vs 1.2).
The APOE epsilon4 allele appears to be associated with a higher prevalence of dementia in PD. Publication bias and heterogeneous source data may, however, confound this conclusion. Confirmatory studies that use standardized and validated diagnostic criteria for dementia in PD are needed.

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    • "The APOE gene polymorphisms are associated with many other diseases. A meta-analysis showed that APOE ϵ4 allele appeared to be associated with a higher prevalence of dementia in Parkinson disease [44]. A meta-analysis suggested that the APOE ϵ4 isoform was a genetic factor that might influence the age at onset of temporal lobe epilepsy [45]. "
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    ABSTRACT: Studies investigating the association between the apolipoprotein E (APOE) gene polymorphism and the risk of intracerebral hemorrhage (ICH) have reported conflicting results. We here performed a meta-analysis based on the evidence currently available from the literature to make a more precise estimation of this relationship. Published literature from the National Library of Medline and Embase databases were retrieved. Odds ratio (OR) and 95% confidence interval (CI) were calculated in fixed- or random-effects models when appropriate. Subgroup analyses were performed by race. This meta-analysis included 11 case-control studies, which included 1,238 ICH cases and 3,575 controls. The combined results based on all studies showed that ICH cases had a significantly higher frequency of APOE epsilon4 allele (OR= 1.42, 95% CI= 1.21,1.67, P<0.001). In the subgroup analysis by race, we also found that ICH cases had a significantly higher frequency of APOE epsilon4 allele in Asians (OR= 1.52, 95% CI= 1.20,1.93, P<0.001) and in Caucasians (OR= 1.34, 95% CI= 1.07,1.66, P=0.009). There was no significant relationship between APOE epsilon2 allele and the risk of ICH. Our meta-analysis suggested that APOE epsilon4 allele was associated with a higher risk of ICH.
    Lipids in Health and Disease 03/2014; 13(1):47. DOI:10.1186/1476-511X-13-47 · 2.22 Impact Factor
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    • "Although not associated with higher PD risk, ApoE ε4 tended to be associated with about 60% higher risk of dementia among PD patients, which was consistent with the previous two meta-analyses: OR=1.6 [95% CI (1.0–2.5)] (Huang, et al., 2006) and 1.74 [95% CI (1.36–2.23), p= 0.0001] (Williams-Gray, et al., 2009). "
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    ABSTRACT: We examined apolipoprotein E (ApoE) genotypes in relation to Parkinson's disease (PD) among 786 cases and 1537 controls, all non-Hispanic Caucasians. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived from multivariate logistic regression models, adjusting for year of birth, sex, smoking status, daily caffeine intake, and family history of PD. Compared with participants with ApoE ε33, ε4 carriers (ε34/ε44) had significantly lower odds for having PD (OR, 0.75; 95% CI, 0.59-0.94; p = 0.01), whereas ε2 carriers (ε23/ε22) did not (OR, 0.95; 95% CI, 0.73-1.24; p = 0.71). Subgroup analyses showed similar results. In addition, we conducted a meta-analysis which confirmed our primary findings (ε34/ε44 vs. ε33: OR, 0.90; 95% CI, 0.81-0.99; p = 0.024 and ε23/ε22 vs. ε33: OR, 1.10; 95% CI, 0.97-1.23; p = 0.13). In PD patients, the prevalence of dementia appeared to be higher among ε4 carriers (compared with ε33: OR, 1.59; 95% CI, 0.98-2.58; p = 0.06), but lower among ε2 carriers (OR, 0.75; 95% CI, 0.40-1.42; p = 0.38), although neither test was statistically significant. Our study suggested that the ApoE ε4 allele may be associated with a lower PD risk among non-Hispanic Caucasians.
    Neurobiology of aging 07/2011; 32(11):2106.e1-6. DOI:10.1016/j.neurobiolaging.2011.05.016 · 5.01 Impact Factor
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    • "Compared to individuals with the E3/3 genotype, E2 carriers had a 20% lower risk of CHD and E4 carriers have a slightly higher risk [23]. In addition to the cardiovascular risk, E4 allele has been found to represent a major risk factor for Alzheimer's disease [24] and a risk factor for dementia in Parkinson disease [25], whereas on the other hand, it has been shown to confer protective effect of up to 40% in age-related macular degeneration [26]. Another meta-analysis suggested that E4 allele affects cognitive performance in healthy aging, although the influence is relatively small and specific to certain domains of cognitive performance [27]. "
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    ABSTRACT: Type 2 diabetes mellitus (T2DM) is a highly complicated metabolic disorder for which there is worldwide effort for the identification of susceptibility genes. Polymorphisms of the Apolipoprotein E (ApoE) gene are associated with plasma lipid and lipoprotein levels and influence cardiovascular risk. Since insulin resistance is known to be strongly associated with metabolic dyslipidemia, ApoE polymorphisms have been implicated in predisposition to diabetes but the results of the individual studies were inconclusive. We present here a meta-analysis of population-based case-control genetic-association studies relating ApoE polymorphisms and T2DM. We included in the analysis 30 studies, which reported data of ApoE genotypes in 5423 T2DM patients and 8197 healthy unrelated controls. Multivariate and univariate methods suggest a significant role played by the E2 allele, since carriers of the E2 allele were at elevated risk for T2DM (Odds Ratio=1.18, 95% CI: 1.02, 1.35). There was no evidence for publication bias or other small-study related bias or significant heterogeneity in the analyses. Cumulative meta-analysis revealed no trend of the effect estimates over time and influential analysis excluded the possibility of a single influential study. E2 allele of ApoE seems to be a moderate risk factor for T2DM. Meta-regression analysis provided some weak evidence that the risk conferred by E2 allele is mediated through altering serum lipid levels (Total Cholesterol, LDL and HDL). Further studies are needed in order to elucidate the metabolic mechanism of this association as well as to study its effects on larger populations.
    Molecular Genetics and Metabolism 03/2010; 100(3):283-91. DOI:10.1016/j.ymgme.2010.03.008 · 2.63 Impact Factor
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