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Lookup NU author(s): Professor Bernard Keavney
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Context: Previous reviews of associations of apolipoprotein E (apoE) genotype and coronary disease have been dominated by smaller studies that are liable to biases. Objective: To reassess associations of apoE genotypes with circulating lipid levels and with coronary risk. Data Sources: We conducted an updated meta-analysis including both published and previously unreported studies, using MEDLINE, EMBASE, BIOSIS, Science Citation Index, and the Chinese National Knowledge Infrastructure Database published between January 1970 and January 2007, reference lists of articles retrieved, and a registry of relevant studies. Study Selection: Eighty-two studies of lipid levels (86 067 healthy participants) and 121 studies of coronary outcomes (37 850 cases and 82 727 controls) were identified, with prespecified principal focus on studies with at least 1000 healthy participants for lipids and those with at least 500 coronary outcomes. Data Extraction: Information on genotype frequencies, lipid levels, coronary outcomes, and laboratory and population characteristics were recorded independently by 2 investigators and/or supplied by study investigators. Results: In the most extreme comparison, people with the ε2/ε2 genotype had 1.14 mmol/L (95% confidence interval [CI], 0.87-1.40 mmol/L [44.0 mg/dL; 95% CI; 33.6-51.1 mg/dL]) or about 31% (95% CI, 23%-38%) lower mean low-density lipoprotein cholesterol (LDL-C) values than those with the ε4/ε4 genotype. There were approximately linear relationships of apoE genotypes (when ordered ε2/ε2, ε2/ε3, ε2/ε4, ε3/ε3, ε3/ε4, ε4/ε4) with LDL-C and with coronary risk. The relationship with high-density lipoprotein cholesterol was inverse and shallow and that with triglycerides was nonlinear and largely confined to the ε2/ε2 genotype. Compared with ε3/ε3, the odds ratio for coronary disease was 0.80 (95% CI, 0.70-0.90) in ε2 carriers and was 1.06 (95% CI, 0.99-1.13) in ε4 carriers. Conclusions: There are approximately linear relationships of apoE genotypes with both LDL-C levels and coronary risk. Compared with individuals with the ε3/ε3 genotype, ε2 carriers have a 20% lower risk of coronary heart disease and ε4 carriers have a slightly higher risk. ©2007 American Medical Association. All rights reserved.
Author(s): Bennet AM, Di Angelantonio E, Ye Z, Wensley F, Dahlin A, Ahlbom A, Keavney B, Collins R, Wiman B, De Faire U, Danesh J
Publication type: Review
Publication status: Published
Journal: Journal of the American Medical Association
Year: 2007
Volume: 298
Issue: 11
Pages: 1300-1311
ISSN (print): 0098-7484
ISSN (electronic): 1538-3598
URL: http://dx.doi.org/10.1001/jama.298.11.1300
DOI: 10.1001/jama.298.11.1300
PubMed id: 17878422
