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26-05-2010 | Cardiology | Article

Gender-specific gene expression found in new-onset HF

Abstract

Free abstract

MedWire News: Researchers have found gender-specific differences in gene expression profiles in endomyocardial biopsy tissue taken from new-onset heart failure (HF) patients.

The findings suggest that inherent factors contribute to gender differences in disease pathophysiology of new-onset HF, and “provide a platform for personalized medicine,” say study authors Joshua Hare (University of Miami, Florida, USA) and colleagues.

The team analyzed biopsy samples from 29 men and 14 women with idiopathic dilated cardiomyopathy and new-onset HF using gene expression microarray technology.

They found 35 genes were overexpressed and 16 downregulated in male compared with female samples.

Most overexpressed transcripts in males were sex-chromosome related, including USP9Y (increased 13-fold), DDX3Y (11-fold), RPS4Y1 (10-fold), and EIF1AY (12-fold). Two autosomal upregulated genes were KCNK1 (1.5-fold) and PLEKHA8 (two-fold) on chromosome 1 and 12, respectively. In addition, CD24 on the Y-chromosome and chromosomes 6 and 15 was upregulated in males (5.6-fold).

In females, the X-chromosome inactivator gene (XIST) was highly upregulated (29-fold), as were X-linked zinc finger proteins (1.9-fold), GATAD1 zinc finger domain on chromosome 7 (1.6-fold), and SLC2A12 on chromosome 4 (1.5-fold).

Given that autoimmunity is implicated in dilated cardiomyopathy, the authors say that the CD24 antigen overexpression in males “is of potential importance because of the well-described lower prevalence of autoimmune disease in males versus females.”

Also, they note, the GATAD1, SLC2A12, and PDE6B upregulation in female versus male samples may explain differences in heart function between genders. GATAD1 associates with adrenergic and angiotensin receptor pathway regulators, SLC2A12 codes for a glucose transporter activated in response to insulin stimulation, and PDE6B is known to modulate inotropic responses and cardioprotective effects.

Furthermore, they suggest that the findings point to potential gender-specific therapeutic targets including KCNK1, which is directly inhibited by ibutilide and type 1a antiarrhythmics, and PDE6B which is inhibited directly by sildenafil and tadalafil.

In a related editorial, Michael Böhm and colleagues (Saarland University, Saarbrücken, Germany) caution that gene expression analyses from biopsies cannot exclude the potential influence of tissue type composition. Here, the proportion of endocardial and myocardial tissue may have differed between the two groups, they say.

Also the editorialists comment that the authors “fail to show differentially regulated clusters of genes which could indicate distinct regulation of functional pathways.”

While Böhm and co-editorialists say the research “brings us further towards treatment approaches that are adjusted to demographic groups,” they are cautious about overplaying its impact on personalized medicine.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

By Caroline Price

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