Adhesion molecule gene variants and plasma protein levels in patients with suspected obstructive sleep apnea

STUDY OBJECTIVES: Untreated obstructive sleep apnea (OSA) patients have an increased risk of cardiovascular disease (CVD). Adhesion molecules, including soluble E-selectin (sE-selectin), intercellular adhesion molecule-1 (ICAM-1), and vascular adhesion molecule-1 (VCAM-1), are associated with incident CVD. We hypothesized that specific genetic variants will be associated with plasma levels of adhesion molecules in suspected OSA patients. We also hypothesized that there may be an interaction between these variants and OSA. METHODS: We measured levels of sE-selectin, sICAM-1 and sVCAM-1 in 491 patients with suspected OSA and genotyped them for 20 polymorphisms. RESULTS: The most significant association was between the ABO rs579459 polymorphism and sE-selectin levels (P = 7×10(−21)), with the major allele T associated with higher levels. The direction of effect and proportion of the variance in sE-selectin levels accounted for by rs579459 (16%) was consistent with estimates from non-OSA cohorts. In a multivariate regression analysis, addition of rs579459 improved the model performance in predicting sE-selectin levels. Three polymorphisms were nominally associated with sICAM-1 levels but none with sVCAM-1 levels. The combination of severe OSA and two rs579459 T alleles identified a group of patients with high sE-selectin levels; however, the increase in sE-selectin levels associated with severe OSA was greater in patients without two T alleles (P = 0.05 test for interaction). CONCLUSIONS: These genetic polymorphisms may help to identify patients at greatest risk of incident CVD and may help in developing a more precision-based approach to OSA care.