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 epsilon 4 allele with the risk of OSA. Design: Random effects meta-analysis and meta-regression Setting: Genetic epidemiological studies reporting the association of APOE epsilon 4 allele with OSA susceptibility. Patients or Participants: Synthesis of APOE epsilon 4 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 epsilon 4 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 (I-2 = 72%, P = 0.001) across study results that was not explained by the mean age, proportion of males, or the proportion possessing the APOE epsilon 4 allele or when grouped based on the geographic location of the study. Conclusions: The hypothesis that the APOE epsilon 4 allele may be causally associated with OSA cannot be supported on the basis of published literature.