Abstract 5903: The Gene Expression Profile of Patients with New Onset Heart Failure Reveals Important Gender Differences
INTRODUCTION: It is increasingly appreciated that gender exerts crucial influences on disease presentation in cardiovascular medicine. We hypothesized that important gender differences in new onset heart failure (HF) occur at the time of disease presentation and performed transcriptomic analysis of endomyocardial biopsies (EMBs) from a cohort of male and female patients with identical type and stage of cardiomyopathy, with similar age, ejection fraction and therapy.
METHODS AND RESULTS: Within a previously described biorepository of 350 EMBs, we selected samples from male (n=29) and female patients (n=14) with IDCM and new onset HF in a case-control fashion. We used the U133 Plus 2.0 microarray (Affymetrix) and Significance Analysis of Microarrays (SAM). There were 33 overexpressed and 16 downregulated genes in male vs female patients (q<2.5%, FC>1.2). In addition to overexpression of Y-chromosome related transcripts (n=10), such as USP9Y (FC>13.1), DDX3Y (FC>11.3), RPS4Y1 (FC>9.9) and EIF1AY (FC>11.8) in males, there was overexpression of CD24 (FC>5.6), recognized for its tyrosine kinase activator potential and KCNK1 (FC>1.5), a potassium channel subfamily member. In females XIST, a transcript for X-chromosome inactivation, was highly overexpressed (FC>28.9), together with X-linked zinc finger proteins (FC>1.9), GATAD1 zinc finger domain (FC>1.6) located on chromosome 7 and phosphodiesterase 6B (FC>1.5) located on chromosome 4. Analysis of a public data set of end stage IDCM (n=15) resulted in ~85% overlap with our findings, including USP9Y, DDX3Y, RPS4Y1, EIF1AY, CD24 and XIST.
CONCLUSION: Transcriptomic analysis of EMBs identified gender specific differences in new onset HF. In addition to disparities that were attributable to sex chromosomes, confirming reliability of the data, we found transcripts that may offer novel insights into gender related differences in the pathophysiology of HF.