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20 July 2004 | Volume 141 Issue 2 | Pages 137-147
Background: Apolipoprotein E (apoE) genotypes play critical roles in lipid metabolism and are believed to influence risk for coronary heart disease (CHD). Despite many population studies, however, the impact of apoE polymorphism on risk for CHD remains uncertain.
Purpose: To qualitatively and quantitatively assess the evidence regarding the relation of apoE polymorphism to CHD risk.
Data Sources: All relevant reports and references from original and review papers published from 1966 to January 2004.
Study Selection: Predefined criteria were used to identify 48 relevant studies.
Data Extraction: A summary database that contained variables of study design, study sample and ethnicity, sex, apoE genotypes, CHD end points, plasma lipid levels, and other CHD risk factors was developed.
Data Synthesis: The authors qualitatively evaluated many potential sources of heterogeneity. To quantify the extent of heterogeneity and assess the consistency of apoE–CHD associations, stratified analyses were conducted using the classic random-effects model. To further incorporate uncertainty due to between-study variation, the pooled odds ratios (ORs) and 95% credible intervals (CrIs) were estimated by using a Bayesian hierarchical model. Finally, the robustness of the pooled estimates was tested in multiple sensitivity analyses. Compared with individuals with the
Limitations: This meta-analysis did not include unpublished data or studies published in languages other than English.
Conclusions: Inadequate statistical power, differences in geographic and ethnic background, allele frequency, sex, CHD phenotypes, study design, and potential gene–environment interactions may have contributed to the conflicting results of previous studies. The apoE
Editors' Notes
Context
Contribution
Implications
–The Editors
Author and Article Information
From Brigham and Women's Hospital, Harvard Medical School, and Harvard School of Public Health, Boston, Massachusetts.
Acknowledgments: The authors thank Sharon-Lise Normand, PhD, from the Department of Biostatistics, Harvard School of Public Health, and Jun S. Liu, PhD, from the Department of Statistics, Harvard University, for their assistance in choosing a proper prior distribution and building the Bayesian hierarchical meta-analysis model.
Grant Support: By the National Institutes of Health (grants DK62290 and HL26490).
Potential Financial Conflicts of Interest: None disclosed.
Requests for Single Reprints: Simin Liu, MD, ScD, Division of Preventive Medicine, Harvard Medical School and Brigham and Women's Hospital, 900 Commonwealth Avenue East, Boston, MA 02215; e-mail, simin.liu{at}channing.harvard.edu.
Current Author Addresses: Drs. Song and Liu: Division of Preventive Medicine, Harvard Medical School and Brigham and Women's Hospital, 900 Commonwealth Avenue East, Boston, MA 02215.
Dr. Stampfer: Department of Epidemiology, Harvard School of Public Health, Kresge Building, 677 Huntington Avenue, Boston, MA 02115. REVIEW
Meta-Analysis: Apolipoprotein E Genotypes and Risk for Coronary Heart Disease
3/3 genotype, carriers of the apoE 4 allele had a 42% higher risk for CHD (OR, 1.42 [95% CrI, 1.26 to 1.61]). The 2 allele had no significant association with CHD risk (OR, 0.98 [CrI, 0.66 to 1.46]). 4 allele is a significant risk factor for CHD.
4 allele had a higher risk for CHD than did persons with the 3/3 genotype. The reviewers found no consistent associations between the 2 allele and CHD risk. They also found that the results of studies sometimes varied because of differences in geographic settings, ethnicity of study samples, allele frequency, CHD phenotypes, and potential gene–environment interactions.
4 allele is probably a risk factor for CHD.
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