Sex- and age-dependent human transcriptome variability: Implications for chronic heart failure

Kenneth R. Boheler, Maria Volkova, Christopher Morrell, Rahul Garg, Yi Zhu, Kenneth Margulies, Anne Marie Seymour, Edward Lakatta

Research output: Contribution to journalArticle

Abstract

Heart failure (HF) is the end result of progressive and diverse biological adaptations within the diseased myocardium. We used cDNA microarrays and quantitative PCR to examine the transcriptomes of 38 left ventricles from failing and nonfailing human myocardium. After identification of a pool of putative HF-responsive candidate genes by microarrays on seven nonfailing and eight failing hearts, we used quantitative PCR and a general linear statistical model in a larger sample set (n = 34) to validate and examine the role of contributing biological variables (age and sex). We find that most HF-candidate genes (transcription factors, Cebpb, Npat; signaling molecules, Map2k3, Map4k5; extracellular matrix proteins, Lum, Cola1; and metabolic enzymes, Mars) demonstrated significant changes in gene expression; however, the majority of differences among samples depended on variables such as sex and age, and not on HF alone. Some HF-responsive gene products also demonstrated highly significant changes in expression as a function of age and/or sex, but independent of HF (Ngp1, Cd163, and Npat). These results emphasize the need to account for biological variables (HF, sex and age interactions) to elucidate genomic correlates that trigger molecular pathways responsible for the progression of HF syndromes.

Original languageEnglish (US)
Pages (from-to)2754-2759
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number5
DOIs
StatePublished - Mar 4 2003
Externally publishedYes

Fingerprint

Transcriptome
Heart Failure
Myocardium
Biological Adaptation
Genes
Mars
Polymerase Chain Reaction
Extracellular Matrix Proteins
Statistical Models
Oligonucleotide Array Sequence Analysis
Heart Ventricles
Linear Models
Transcription Factors
Gene Expression
Enzymes

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Sex- and age-dependent human transcriptome variability : Implications for chronic heart failure. / Boheler, Kenneth R.; Volkova, Maria; Morrell, Christopher; Garg, Rahul; Zhu, Yi; Margulies, Kenneth; Seymour, Anne Marie; Lakatta, Edward.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 100, No. 5, 04.03.2003, p. 2754-2759.

Research output: Contribution to journalArticle

Boheler, Kenneth R. ; Volkova, Maria ; Morrell, Christopher ; Garg, Rahul ; Zhu, Yi ; Margulies, Kenneth ; Seymour, Anne Marie ; Lakatta, Edward. / Sex- and age-dependent human transcriptome variability : Implications for chronic heart failure. In: Proceedings of the National Academy of Sciences of the United States of America. 2003 ; Vol. 100, No. 5. pp. 2754-2759.
@article{57860deab84c4e7481a1a4d4b7f841b6,
title = "Sex- and age-dependent human transcriptome variability: Implications for chronic heart failure",
abstract = "Heart failure (HF) is the end result of progressive and diverse biological adaptations within the diseased myocardium. We used cDNA microarrays and quantitative PCR to examine the transcriptomes of 38 left ventricles from failing and nonfailing human myocardium. After identification of a pool of putative HF-responsive candidate genes by microarrays on seven nonfailing and eight failing hearts, we used quantitative PCR and a general linear statistical model in a larger sample set (n = 34) to validate and examine the role of contributing biological variables (age and sex). We find that most HF-candidate genes (transcription factors, Cebpb, Npat; signaling molecules, Map2k3, Map4k5; extracellular matrix proteins, Lum, Cola1; and metabolic enzymes, Mars) demonstrated significant changes in gene expression; however, the majority of differences among samples depended on variables such as sex and age, and not on HF alone. Some HF-responsive gene products also demonstrated highly significant changes in expression as a function of age and/or sex, but independent of HF (Ngp1, Cd163, and Npat). These results emphasize the need to account for biological variables (HF, sex and age interactions) to elucidate genomic correlates that trigger molecular pathways responsible for the progression of HF syndromes.",
author = "Boheler, {Kenneth R.} and Maria Volkova and Christopher Morrell and Rahul Garg and Yi Zhu and Kenneth Margulies and Seymour, {Anne Marie} and Edward Lakatta",
year = "2003",
month = "3",
day = "4",
doi = "10.1073/pnas.0436564100",
language = "English (US)",
volume = "100",
pages = "2754--2759",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "5",

}

TY - JOUR

T1 - Sex- and age-dependent human transcriptome variability

T2 - Implications for chronic heart failure

AU - Boheler, Kenneth R.

AU - Volkova, Maria

AU - Morrell, Christopher

AU - Garg, Rahul

AU - Zhu, Yi

AU - Margulies, Kenneth

AU - Seymour, Anne Marie

AU - Lakatta, Edward

PY - 2003/3/4

Y1 - 2003/3/4

N2 - Heart failure (HF) is the end result of progressive and diverse biological adaptations within the diseased myocardium. We used cDNA microarrays and quantitative PCR to examine the transcriptomes of 38 left ventricles from failing and nonfailing human myocardium. After identification of a pool of putative HF-responsive candidate genes by microarrays on seven nonfailing and eight failing hearts, we used quantitative PCR and a general linear statistical model in a larger sample set (n = 34) to validate and examine the role of contributing biological variables (age and sex). We find that most HF-candidate genes (transcription factors, Cebpb, Npat; signaling molecules, Map2k3, Map4k5; extracellular matrix proteins, Lum, Cola1; and metabolic enzymes, Mars) demonstrated significant changes in gene expression; however, the majority of differences among samples depended on variables such as sex and age, and not on HF alone. Some HF-responsive gene products also demonstrated highly significant changes in expression as a function of age and/or sex, but independent of HF (Ngp1, Cd163, and Npat). These results emphasize the need to account for biological variables (HF, sex and age interactions) to elucidate genomic correlates that trigger molecular pathways responsible for the progression of HF syndromes.

AB - Heart failure (HF) is the end result of progressive and diverse biological adaptations within the diseased myocardium. We used cDNA microarrays and quantitative PCR to examine the transcriptomes of 38 left ventricles from failing and nonfailing human myocardium. After identification of a pool of putative HF-responsive candidate genes by microarrays on seven nonfailing and eight failing hearts, we used quantitative PCR and a general linear statistical model in a larger sample set (n = 34) to validate and examine the role of contributing biological variables (age and sex). We find that most HF-candidate genes (transcription factors, Cebpb, Npat; signaling molecules, Map2k3, Map4k5; extracellular matrix proteins, Lum, Cola1; and metabolic enzymes, Mars) demonstrated significant changes in gene expression; however, the majority of differences among samples depended on variables such as sex and age, and not on HF alone. Some HF-responsive gene products also demonstrated highly significant changes in expression as a function of age and/or sex, but independent of HF (Ngp1, Cd163, and Npat). These results emphasize the need to account for biological variables (HF, sex and age interactions) to elucidate genomic correlates that trigger molecular pathways responsible for the progression of HF syndromes.

UR - http://www.scopus.com/inward/record.url?scp=0037418307&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037418307&partnerID=8YFLogxK

U2 - 10.1073/pnas.0436564100

DO - 10.1073/pnas.0436564100

M3 - Article

C2 - 12601168

AN - SCOPUS:0037418307

VL - 100

SP - 2754

EP - 2759

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 5

ER -