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非缺血性人类心力衰竭中心肌基因表达的性别和年龄二态性

Sex and age dimorphism of myocardial gene expression in nonischemic human heart failure.

作者信息

Fermin David R, Barac Ana, Lee Sangjin, Polster Sean P, Hannenhalli Sridhar, Bergemann Tracy L, Grindle Suzanne, Dyke David B, Pagani Francis, Miller Leslie W, Tan Sarah, Dos Remedios Cris, Cappola Thomas P, Margulies Kenneth B, Hall Jennifer L

机构信息

Lillehei Heart Institute, Division of Cardiology, Developmental Biology Center, University of Minnesota, Minneapolis, USA.

出版信息

Circ Cardiovasc Genet. 2008 Dec;1(2):117-25. doi: 10.1161/CIRCGENETICS.108.802652. Epub 2008 Dec 9.

Abstract

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.

摘要

背景

我们报告了对102例扩张型心肌病患者左心室样本中基因表达差异按性别和年龄进行的首次全面分析。

方法与结果

对来自3个不同中心的30名女性和72名男性的基因表达数据(HG-U133A基因芯片,Affymetrix公司)进行了分析。超过1800个基因在心脏中表现出性别差异(校正P值<0.05)。这些基因中有相当数量在参与离子转运和G蛋白偶联受体信号传导的基因本体途径中高度富集。这些基因的定位显示在性染色体以及3号、4号和14号染色体上均有富集。本研究的第二个目标是确定年龄对基因表达的影响。在女性队列中,与55岁以上年龄组相比,55岁以下年龄组中有超过140个基因差异表达。这些基因在参与DNA损伤的基因本体途径中高度富集。相比之下,55岁以下男性队列与55岁以上年龄组相比,没有基因达到统计学显著差异。

结论

扩张型心肌病中的基因表达显示出与其他体细胞组织相似的性别差异以及女性队列中的年龄差异证据。

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