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Keywords:

  • atherosclerosis;
  • biomarker;
  • CD93;
  • expression;
  • genetics;
  • myocardial infarction

Abstract.  Mälarstig A, Silveira A, Wågsäter D, Öhrvik J, Bäcklund A, Samnegård A, Khademi M, Hellenius M-L, Leander K, Olsson T, Uhlén M, de Faire U, Eriksson P, Hamsten A (Karolinska University Hospital; Institute of Environmental Medicine, Karolinska Institutet, Stockholm; KTH-Royal Institute of Technology, Stockholm, Sweden). Plasma CD93 concentration is a potential novel biomarker for coronary artery disease. J Intern Med 2011; 270: 229–236.

Objectives.  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.

Methods and Results.  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).

Conclusion.  The results of the present study suggest that the concentration of soluble CD93 in plasma is a potential novel biomarker for CAD, including MI.