Department of Epidemiology, Box 357236, University of Washington, Seattle, Washington 98195, USA.
Arterioscler Thromb Vasc Biol. 2013 Jan;33(1):158-64. doi: 10.1161/ATVBAHA.112.300421. Epub 2012 Nov 15.
CD14 is a glycosylphosphotidylinositol-anchored membrane glycoprotein expressed on neutrophils and monocytes/macrophages that also circulates as a soluble form (sCD14). Despite the well-recognized role of CD14 in inflammation, relatively little is known about the genetic determinants of sCD14 or the relationship of sCD14 to vascular- and aging-related phenotypes.
We measured baseline levels of sCD14 in >5000 European-American and black adults aged 65 years and older from the Cardiovascular Health Study, who were well characterized at baseline for atherosclerotic risk factors and subclinical cardiovascular disease, and who have been followed for clinical cardiovascular disease and mortality outcomes up to 20 years. At baseline, sCD14 generally showed strong positive correlations with traditional cardio-metabolic risk factors and with subclinical measures of vascular disease such as carotid wall thickness and ankle-brachial index (independently of traditional cardiovascular disease risk factors), and was also inversely correlated with body mass index. In genomewide association analyses of sCD14, we (1) confirmed the importance of the CD14 locus on chromosome 5q21 in European-American; (2) identified a novel African ancestry-specific allele of CD14 associated with lower sCD14 in blacks; and (3) identified a putative novel association in European-American of a nonsynonymous variant of PIGC, which encodes an enzyme required for the first step in glycosylphosphotidylinositol anchor biosynthesis. Finally, we show that, like other acute phase inflammatory biomarkers, sCD14 predicts incident cardiovascular disease, and strongly and independently predicts all-cause mortality in older adults.
CD14 independently predicts risk mortality in older adults.
CD14 是一种糖基磷脂酰肌醇锚定的膜糖蛋白，表达于中性粒细胞和单核细胞/巨噬细胞，也以可溶性形式（sCD14）循环。尽管 CD14 在炎症中作用得到广泛认可，但关于 sCD14 的遗传决定因素或 sCD14 与血管和衰老相关表型的关系知之甚少。
我们在心血管健康研究中测量了超过 5000 名年龄在 65 岁及以上的欧洲裔和黑人成年人的 sCD14 基线水平，这些成年人在基线时具有动脉粥样硬化危险因素和亚临床心血管疾病的良好特征，并且已经随访了长达 20 年的临床心血管疾病和死亡率结局。在基线时，sCD14 通常与传统的心血管代谢危险因素以及血管疾病的亚临床测量（如颈动脉壁厚度和踝臂指数）呈强正相关（独立于传统心血管疾病危险因素），并且与体重指数呈负相关。在 sCD14 的全基因组关联分析中，我们（1）证实了 5q21 染色体上的 CD14 基因座在欧洲裔人群中的重要性；（2）鉴定出一种与黑人 sCD14 水平较低相关的新型非洲裔特异性 CD14 等位基因；（3）在欧洲裔人群中鉴定出一种 PIGC 的非同义变异的假定新关联，该基因编码糖基磷脂酰肌醇锚生物合成第一步所需的酶。最后，我们表明，像其他急性相炎症生物标志物一样，sCD14 预测心血管疾病的发生，并在老年人中强烈且独立地预测全因死亡率。
CD14 独立预测老年人的死亡风险。
