Published Online
on December 9, 2008

A more recent version of this article appeared on December 1, 2008

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Original Article

Sex and Age Dimorphism of Myocardial Gene Expression in Nonischemic Human Heart Failure

David R. Fermin¹; Ana Barac²; Sangjin Lee¹; Sean P. Polster¹; Sridhar Hannenhalli³; Tracy Bergemann¹; Suzanne M. Grindle¹; David B. Dyke⁴; Francis D. Pagani⁴; Leslie W. Miller²; Sara Tan⁵; Cris dos Remedios⁵; Thomas P. Cappola³; Kenneth B. Margulies³ and Jennifer L. Hall^1,6

¹ University of Minnesota, Minneapolis, MN;
² Washington Hospital Center, Washington, DC;
³ University of Pennsylvania, Philadelphia, PA;
⁴ University of Michigan, Ann Arbor, MI;
⁵ University of Sydney, Sydney, Australia

⁶ E-mail: jlhall{at}umn.edu

Background—We report the first comprehensive analysis of gene expression differences by sex and age in left ventricular samples from 102 patients with dilated cardiomyopathy.

Methods and Results—Gene expression data (HG-U133A gene chip, Affymetrix) were analyzed from 30 females and 72 males from 3 separate centers. Over 1,800 genes displayed sexual dimorphism in the heart (adjusted p-value <0.05). A significant number of these genes were highly represented in gene ontology pathways involved in ion transport and G-protein-coupled receptor signaling. Localization of these genes revealed enrichment on both the sex chromosomes as well as chromosomes 3, 4, and 14. The second goal of this study was to determine the effect of age on gene expression. Within the female cohort, over 140 genes were differentially expressed in the under 55 age group compared to age group above 55 years of age. These genes were highly represented in gene ontology pathways involved in DNA damage. In contrast, zero genes in the male cohort under age 55 met statistical significance when compared to the group over 55.

Conclusions—Gene expression in dilated cardiomyopathy displayed evidence of sexual dimorphism similar to other somatic tissues and age dimorphism within the female cohort.

Key Words: aging • genes • heart failure • sex

Author contributions: David R. Fermin and Ana Barac contributed equally to this work.