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

OBSTRUCTIVE SLEEP APNEA (OSA)—DEFINED AS EPISODIC AND REPETITIVE NARROWING OF UPPER AIRWAYS ACCOMPANIED BY LOSS OF TONE IN THE pharyngeal musculature leading to sleep disturbances such as snoring, frequent arousals, and daytime sleepiness—is widely prevalent at all ages and is associated with concomitant or consequential cardiovascular morbidities and obesity, disorders known to have a genetic basis.1–7 Since wide inter-individual variations exist in regards to the onset, severity, and the comorbidity mosaic of OSA, it is being increasingly argued that this condition may have a genetic component.8–10 However, the current understanding of the genetic basis of OSA is cursory. Over the last decade, several investigators have evaluated the potential association between OSA and polymorphisms in the apolipoprotein E (APOE) gene.11–18 These genetic epidemiological studies attempted to build on the observations that the apoE molecule is implicated in the causation of Alzheimer disease,19,20 atherosclerosis,1,4 and HIV-associated dementia,21 owing to its role in cholesterol transport and metabolism.22 It is argued that the apoE macromolecule, consequent to its central nervous effects, may play a role in maintaining the muscle tone of pharyngeal muscle,17 and thus the APOE polymorphisms that can modulate gene expression may have bearing on OSA susceptibility. Of interest, the APOE e4 allele has been the most intensely scrutinized one in the context of OSA. However, the exact biological mechanism and epidemiological contribution of APOE polymorphisms in OSA is still a matter of contention. Therefore, we report our results of a meta-analytic synthesis summarizing the strength of association of the APOE e4 allele with susceptibility to OSA.