The gene expression profile of patients with new-onset heart failure reveals important gender-specific differences

Bettina Heidecker, Guillaume Lamirault, Edward K. Kasper, Ilan S. Wittstein, Hunter C. Champion, Elayne Breton, Stuart D. Russell, Jennifer Hall, Michelle M. Kittleson, Kenneth L. Baughman, Joshua M. Hare

Research output: Contribution to journalArticle

Abstract

AimsWe sought to test the hypothesis that inherent biological factors contribute to gender differences in disease pathophysiology of new-onset heart failure (HF), which can be detected from the transcriptome of a single endomyocardial biopsy (EMB).Methods and resultsWe analysed samples from male (n = 29) and female patients (n = 14) with idiopathic dilated cardiomyopathy (IDCM) and new-onset HF with U133 Plus 2.0 microarrays (Affymetrix) and significance analysis of microarrays (SAM). There were 35 overexpressed and 16 downregulated transcripts in men vs. women [q < 5, fold change (FC) > 1.2]. In addition to overexpression of Y-chromosome-related transcripts (n = 18), 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) and KCNK1 (FC > 1.5). In females, XIST was highly overexpressed (FC > 28.9), together with X-linked zinc finger proteins (FC > 1.9) and autosomal genes GATAD1 (FC > 1.6), SLC2A12 (FC > 2.9), and PDE6B (FC > 1.5). Analysis of a public data set of end-stage IDCM (n = 15) resulted in ∼85 overlap with our findings. Conclusion This is the first study that identified gender-specific transcriptomic differences in new-onset HF. Our findings may offer novel insights into fundamental biological differences in the pathophysiology of HF between sexes and provide a platform for personalized medicine.

Original languageEnglish (US)
Pages (from-to)1188-1196
Number of pages9
JournalEuropean heart journal
Volume31
Issue number10
DOIs
StatePublished - May 2010

Keywords

  • Cardiomyopathy
  • Gender
  • Gene expression
  • Heart failure
  • Transcriptomics

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Heidecker, B., Lamirault, G., Kasper, E. K., Wittstein, I. S., Champion, H. C., Breton, E., Russell, S. D., Hall, J., Kittleson, M. M., Baughman, K. L., & Hare, J. M. (2010). The gene expression profile of patients with new-onset heart failure reveals important gender-specific differences. European heart journal, 31(10), 1188-1196. https://doi.org/10.1093/eurheartj/ehp549