Copy Number Variations in Serum Amyloid A Play a Role in the Determination of its Individual Baseline Concentrations

To the Editor: Serum amyloid A (SAA), including SAA1 and SAA2 , is not only an acute-phase reactant but also an apolipoprotein involved in the pathogenesis of atherosclerosis. A moderate increase in the concentration of SAA is thought to be an indicator of chronic systemic inflammation that plays an important role in the initiation and progression of cardiovascular disease (CVD) (1). However, prospective studies have shown conflicting results regarding moderately increased concentrations of SAA as a risk factor of CVD (2). It is also noteworthy that the reported physiological SAA concentrations varied substantially from 0.1 to 40 mg/L, which reflects the heterogeneity of SAA baseline concentrations (1). This heterogeneity could be a major obstacle for the applicability of SAA as a prognostic factor of CVD in clinical practice. Twin studies suggest that there is a substantial genetic contribution to SAA baseline concentrations, with heritability estimates of 59% (95% CI: 49–67%) (3). Recently, like other types of genetic variation, the impact of submicroscopic gene copy number variations (CNVs) on human diseases has been investigated and found to be associated with susceptibility or resistance to many diseases (4). Because the aim of this study was to identify the association …