Lack of Association of the APOE ε4 Allele with the Risk of Obstructive Sleep Apnea: Meta-Analysis and Meta-Regression

STUDY OBJECTIVES: Reports on the association of polymorphisms in the gene encoding apolipoprotein E (APOE)--a vital macromolecule in cholesterol metabolism--with obstructive sleep apnea (OSA) have provided conflicting results. Our objective was to meta-analytically synthesize the existing evidence for the association of the APOE epsilon4 allele with the risk of OSA. DESIGN: Random effects meta-analysis and meta-regression. SETTING: Genetic epidemiological studies reporting the association of APOE epsilon4 allele with OSA susceptibility. PATIENTS OR PARTICIPANTS: Synthesis of APOE epsilon4 allele data from 6,508 subjects including 1,901 cases of OSA and 4,607 controls. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Eight studies were included in the random effects meta-analysis; the summary effect size measured as odds ratio (OR) for association of the APOE epsilon4 allele with the risk of OSA was found to be 1.13 (95% confidence interval 0.86-1.47). There was a statistically significant heterogeneity (I2 = 72%, P = 0.001) across study results that was not explained by the mean age, proportion of males, or the proportion possessing the APOE epsilon4 allele or when grouped based on the geographic location of the study. CONCLUSIONS: The hypothesis that the APOE epsilon4 allele may be causally associated with OSA cannot be supported on the basis of published literature.