Centre for Heart Lung Innovation, St. Paul's Hospital and University of British Columbia, Vancouver, British Columbia, Canada.
UBC Hospital Sleep Disorders Program, Division of Respiratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
PLoS One. 2019 Jan 17;14(1):e0210732. doi: 10.1371/journal.pone.0210732. eCollection 2019.
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.
未经治疗的阻塞性睡眠呼吸暂停（OSA）患者发生心血管疾病（CVD）的风险增加。黏附分子，包括可溶性 E-选择素（sE-选择素）、细胞间黏附分子-1（ICAM-1）和血管细胞黏附分子-1（VCAM-1），与 CVD 的发生有关。我们假设特定的遗传变异与疑似 OSA 患者的黏附分子血浆水平相关。我们还假设这些变异与 OSA 之间可能存在相互作用。
我们测量了 491 例疑似 OSA 患者的 sE-选择素、sICAM-1 和 sVCAM-1 水平，并对其进行了 20 个多态性的基因分型。
ABO rs579459 多态性与 sE-选择素水平之间的相关性最强（P = 7×10-21），主要等位基因 T 与较高水平相关。rs579459 对 sE-选择素水平的影响方向和变异比例（16%）与非 OSA 队列的估计值一致。在多变量回归分析中，加入 rs579459 可提高预测 sE-选择素水平的模型性能。有 3 个多态性与 sICAM-1 水平有显著相关性，但与 sVCAM-1 水平无关。严重 OSA 和 rs579459 两个 T 等位基因的组合确定了一组 sE-选择素水平较高的患者；然而，与严重 OSA 相关的 sE-选择素水平增加在没有两个 T 等位基因的患者中更大（P = 0.05 检验交互作用）。
这些遗传多态性可能有助于识别发生 CVD 风险最高的患者，并有助于开发更基于精准的 OSA 护理方法。
