Observational studySleep & breathing = Schlaf & Atmung2026
The COMT rs4680 SNP participates in the regulation of the arousal threshold in patients with obstructive sleep apnea.
Observational study in Sleep & breathing = Schlaf & Atmung, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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10 authors.
Funding
Abstract
purposeTo investigate whether the functional catechol-O-methyltransferase (COMT) rs4680 polymorphism is related to a predicted low respiratory arousal threshold (LAT) phenotype in adults with polysomnography-confirmed obstructive sleep apnea (OSA), and to assess selected dopaminergic pathway-related polymorphisms.
methodsIn this prospective observational study, 144 adults with OSA underwent polysomnography. LAT was estimated non-invasively using the Edwards criteria based on apnea-hypopnea index < 30 events/h, nadir oxygen saturation > 82.5%, and hypopnea fraction > 58.3%, with LAT defined by fulfillment of at least two criteria. Peripheral blood samples were genotyped for COMT rs4680, COMT rs6269, DRD1 rs686, and a DRD2 variant.
resultsAmong the 144 participants, 76 (52.8%) met criteria for LAT and 68 (47.2%) for non-LAT. Compared with non-LAT patients, the LAT group was younger and showed lower OSA severity markers, including lower apnea-hypopnea index, oxygen desaturation index, apnea indices, snoring burden, and time with oxygen saturation < 90%, together with higher mean and minimum oxygen saturation. The arousal index was also lower in the LAT group (4.40 vs. 9.42/h, p = 0.006). A differential distribution of COMT rs4680 genotypes was observed between LAT and non-LAT groups, with G-allele-containing genotypes more frequent in LAT, whereas the AA genotype was more common in non-LAT patients. No association was found for the other analyzed polymorphisms.
conclusionThese findings suggest that COMT rs4680 may be associated with the predicted LAT phenotype in OSA, supporting the concept that dopaminergic pathways may contribute to OSA endotypic heterogeneity. Given the indirect definition of LAT and the candidate-gene design, the results should be considered hypothesis-generating and require replication.
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