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


RESULTS
We 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 approximately 85% overlap with our findings.


CONCLUSIONS
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.
Heidecker
Bettina
B
Interdisciplinary Stem Cell Institute, University of Miami, Miller School of Medicine, Biomedical Research, Miami, FL 33101, USA.
Lamirault
Guillaume
G
Kasper
Edward K
EK
Wittstein
Ilan S
IS
Champion
Hunter C
HC
Breton
Elayne
E
Russell
Stuart D
SD
Hall
Jennifer
J
Kittleson
Michelle M
MM
Baughman
Kenneth L
KL
Hare
Joshua M
JM
D000328:Adult; D015153:Blotting, Western; D002311:Cardiomyopathy, Dilated / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006333:Heart Failure / Q000235:genetics*; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors; D013318:Stroke Volume / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
D014157:Transcription Factors