Metabolic Research Unit, Deakin University, Geelong 3217, Australia.
J Clin Endocrinol Metab. 2010 May;95(5):2476-85. doi: 10.1210/jc.2010-0042. Epub 2010 Mar 17.
Chemerin is a new adipokine associated with obesity and the metabolic syndrome. Gene expression levels of chemerin were elevated in the adipose depots of obese compared with lean animals and was markedly elevated during differentiation of fibroblasts into mature adipocytes.
The objective of the study was to identify factors that affect the regulation and potential function of chemerin using a genetics approach.
DESIGN, SETTING, PATIENTS, AND INTERVENTION: Plasma chemerin levels were measured in subjects from the San Antonio Family Heart Study, a large family-based genetic epidemiological study including 1354 Mexican-American individuals. Individuals were randomly sampled without regard to phenotype or disease status.
A genome-wide association analysis using 542,944 single-nucleotide polymorphisms in a subset of 523 of the same subjects was undertaken. The effect of chemerin on angiogenesis was measured using human endothelial cells and interstitial cells in coculture in a specially formulated medium.
Serum chemerin levels were found to be highly heritable (h(2) = 0.25; P = 1.4 x 10(-9)). The single-nucleotide polymorphism showing strongest evidence of association (rs347344; P = 1.4 x 10(-6)) was located within the gene encoding epithelial growth factor-like repeats and discoidin I-like domains 3, which has a known role in angiogenesis. Functional angiogenesis assays in human endothelial cells confirmed that chemerin significantly mediated the formation of blood vessels to a similar extent as vascular endothelial growth factor.
Here we demonstrate for the first time that plasma chemerin levels are significantly heritable and identified a novel role for chemerin as a stimulator of angiogenesis.
趋化素是一种与肥胖和代谢综合征相关的新型脂肪因子。与瘦动物相比，肥胖动物脂肪组织中趋化素的基因表达水平升高，并且在成纤维细胞分化为成熟脂肪细胞的过程中明显升高。
本研究旨在通过遗传方法鉴定影响趋化素调节和潜在功能的因素。
设计、地点、患者和干预：在圣安东尼奥家族心脏研究中测量了来自受试者的血浆趋化素水平，这是一项包括 1354 名墨西哥裔美国人的大型基于家族的遗传流行病学研究。个体是随机抽样的，不考虑表型或疾病状态。
在 523 名相同受试者的亚组中使用 542944 个单核苷酸多态性进行全基因组关联分析。使用特别配制的培养基中的人内皮细胞和间质细胞共培养来测量趋化素对血管生成的影响。
发现血清趋化素水平具有高度遗传性（h²=0.25；P=1.4×10⁻⁹）。与趋化素关联最强的单核苷酸多态性（rs347344；P=1.4×10⁻⁶）位于编码上皮生长因子样重复和盘状结构域 I 样结构域 3 的基因内，该基因已知在血管生成中具有作用。在人内皮细胞中的功能性血管生成测定证实，趋化素与血管内皮生长因子一样，显著介导血管形成。
我们首次证明了血浆趋化素水平具有显著的遗传性，并确定了趋化素作为血管生成刺激物的新作用。
