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Published ahead of print on June 23, 2004, doi:10.1164/rccm.200312-1686OC
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American Journal of Respiratory and Critical Care Medicine Vol 170. pp. 911-919, (2004)
© 2004 American Thoracic Society
doi: 10.1164/rccm.200312-1686OC

Gene Microarray Analysis of Peripheral Blood Cells in Pulmonary Arterial Hypertension

Todd M. Bull, Christopher D. Coldren, Mark Moore, Sylk M. Sotto-Santiago, David V. Pham, S. Patrick Nana-Sinkam, Norbert F. Voelkel and Mark W. Geraci

Pulmonary Hypertension Center, Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver, Colorado

Correspondence and requests for reprints should be addressed to Todd M. Bull, M.D., Division of Pulmonary Sciences and Critical Care Medicine, 4200 East 9th Avenue, Denver, CO 80262. Email: todd.bull{at}uchsc.edu

The importance of genetic predisposition, inflammation, and autoimmune mechanisms in the development of pulmonary arterial hypertension (PAH) is becoming increasingly clear. We hypothesized that the analysis of gene expression profiles from peripheral blood mononuclear cells would distinguish patients with PAH from normal volunteers. We also hypothesized that a subset of genes would discriminate between patients with idiopathic PAH and pulmonary hypertension related to secondary causes. Mononuclear cells were isolated from 15 patients diagnosed with PAH and 6 normal control subjects. Microarray expression was performed, and the expression profiles were analyzed for consistent and predictive differences in gene expression. We identified a signature set of 106 genes that discriminated with high certainty (p <= 0.002) between patients with PAH and normal individuals. The results of the microarray analysis were retrospectively and prospectively confirmed by quantitative polymerase chain reaction for 2 of the 106 genes. Supervised clustering analysis generated a list of differentially expressed genes between patients with idiopathic and secondary causes of pulmonary hypertension. Microarray expression profiling of peripheral blood cells can discriminate between patients with PAH and normal volunteers. These findings may have important implications toward diagnosis, screening, and pathogenesis of this disease.

Key Words: biomarker • gene microarray • inflammation • mononuclear cells • pulmonary arterial hypertension




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