Date Published: January 17, 2019
Publisher: Public Library of Science
Author(s): Andrew J. Sandford, Amanda Ha, David A. Ngan, Loubna Akhabir, Aabida Saferali, Nurit Fox, A. J. Hirsch Allen, Simon C. Warby, Stephan F. van Eeden, Najib T. Ayas, Yoshiaki Taniyama.
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.
We measured levels of sE-selectin, sICAM-1 and sVCAM-1 in 491 patients with suspected OSA and genotyped them for 20 polymorphisms.
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).
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.
Obstructive sleep apnea (OSA), characterized by recurrent collapse of the upper airway during sleep, is a common under-diagnosed disease that causes serious individual and population health consequences. Untreated OSA can cause disabling symptoms, increase health care utilization, lead to automobile crashes and injuries, and to premature death . In a community-based study of middle-aged subjects, 9% of men and 4% of women had moderate to severe OSA (i.e., apnea hypopnea index (AHI) ≥15/hr) . Based upon the subsequent increased prevalence of obesity, current estimated OSA rates are 14–55% higher . The vast majority of patients have not been clinically diagnosed .
In our cohort of patients with suspected OSA, we found significant associations between various SNPs and levels of CAMs. This was especially robust for sE-selectin, where the T allele of rs579459 was associated with increased levels. Both sleep apnea severity (as assessed by AHI) and rs579459 were significantly correlated with sE-selectin levels, and there was an interaction between these two variables. Specifically, the increase in sE-selectin levels associated with severe OSA was greater in patients without the TT genotype, although the combination of severe OSA and the TT polymorphism identified a group of patients with high sE-selectin levels. Given the relationship between sE-selectin levels and cardiac events, rs579459 may help to identify patients at greatest risk of incident CVD. Ironically, the impact of OSA treatment might be greater in patients without the TT genotype. Nevertheless, the interaction between the rs579459 TT genotype and severe OSA was of borderline statistical significance and therefore should be viewed with caution until verified in another population.