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

From the Lillehei Heart Institute, Division of Cardiology (D.R.F., S.L., S.P.P., S.G., J.L.H.), Developmental Biology Center (J.L.H.), University of Minnesota, Minneapolis; Washington Hospital Center (A.B., L.W.M.), Washington DC; University of Pennsylvania (S.H., T.P.C., K.B.M.), Philadelphia; Division of Biostatistics (T.L.B.), School of Public Health, University of Minnesota, Minneapolis; University of Michigan (D.B.D, F.P.), Ann Arbor; and the Department of Anatomy and Histology (S.T., C.R.), University of Sydney, Australia.

Correspondence to Jennifer L. Hall, Division of Cardiology, Lillehei Heart Institute, 312 Church St, Minneapolis, MN 55455. E-mail jlhall{at}umn.edu

Received July 22, 2008; accepted October 14, 2008.

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. More than 1800 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, >140 genes were differentially expressed in the <55 years age group compared with the >55 years age group. These genes were highly represented in gene ontology pathways involved in DNA damage. In contrast, zero genes in the male cohort <55 years met statistical significance when compared with the >55 years age group.

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

The online-only Data Supplement is available at http://circgenetics.ahajournals.org/cgi/content/full/CIRCGENETICS.108.802652/DC1.

Drs Fermin and Barac contributed equally to this work.