Atherosclerosis Research Unit, Karolinska University Hospital, Stockholm, Sweden.
J Intern Med. 2011 Sep;270(3):229-36. doi: 10.1111/j.1365-2796.2011.02364.x. Epub 2011 Mar 21.
A common nonsynonymous single nucleotide polymorphism (SNP) in the CD93 gene (rs3746731, Pro541Ser) has been associated with risk of coronary artery disease (CAD). CD93 is a transmembrane glycoprotein, which is detectable in soluble form in human plasma. We investigated whether the concentration of soluble CD93 in plasma is related to risk of myocardial infarction (MI) and CAD, using a case-control study of premature MI (n = 764) and a nested case-control analysis of a longitudinal cohort study of 60-year-old subjects (analysis comprising 844 of 4232 subjects enrolled at baseline). In addition, SNPs in the CD93 gene were studied in relation to plasma CD93 concentration and CD93 mRNA expression.
A sensitive and specific enzyme-linked immunosorbent assay was established for determination of the plasma CD93 concentration. Subjects were divided into three groups according to tertiles of the distribution of CD93 concentration. Lower odds ratios for risk of MI and incidence of CAD were observed in the middle CD93 tertile (142-173 μg L(-1) ): odds ratio (95% confidence interval), 0.69 (0.49-0.97) and 0.61 (0.40-0.94), respectively. These associations were independent of traditional CAD risk factors. The minor allele of a SNP in the 3' untranslated region of CD93 (rs2749812) was associated with increased plasma CD93 concentrations (P = 0.03) and increased CD93 mRNA expression levels (P = 0.02).
The results of the present study suggest that the concentration of soluble CD93 in plasma is a potential novel biomarker for CAD, including MI.
CD93 基因（rs3746731，脯氨酸 541 丝氨酸）中的一个常见非同义单核苷酸多态性（SNP）与冠心病（CAD）的风险相关。CD93 是一种跨膜糖蛋白，可在人血浆中以可溶性形式检测到。我们通过对早发性心肌梗死（MI）病例对照研究（n=764）和 60 岁受试者的纵向队列研究的嵌套病例对照分析（分析包括 4232 名入组时的受试者中的 844 名），研究了血浆可溶性 CD93 浓度与 MI 和 CAD 风险的关系。此外，还研究了 CD93 基因中的 SNP 与血浆 CD93 浓度和 CD93 mRNA 表达的关系。
建立了一种用于测定血浆 CD93 浓度的敏感和特异的酶联免疫吸附测定法。根据 CD93 浓度分布的三分位，将受试者分为三组。中间 CD93 三分位（142-173μg/L）的 MI 风险和 CAD 发生率的比值较低：比值比（95%置信区间）为 0.69（0.49-0.97）和 0.61（0.40-0.94）。这些关联独立于传统的 CAD 危险因素。CD93 3'非翻译区的 SNP（rs2749812）的次要等位基因与血浆 CD93 浓度增加（P=0.03）和 CD93 mRNA 表达水平增加（P=0.02）相关。
本研究结果表明，血浆可溶性 CD93 浓度可能是 CAD（包括 MI）的一个潜在新型生物标志物。
