Journal
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
Volume 170, Issue 8, Pages 911-919Publisher
AMER THORACIC SOC
DOI: 10.1164/rccm.200312-1686OC
Keywords
biomarker; gene microarray; inflammation; mononuclear cells; pulmonary arterial hypertension
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Funding
- NHLBI NIH HHS [P01 HL 66254, R01 HL 72340] Funding Source: Medline
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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 less than or equal to 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.
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