Is a diabetes mellitus-linked amino acid signature associated with β-blocker-induced impaired fasting glucose

Rhonda M. Cooper-DeHoff, Wei Hou, Liming Weng, Rebecca A. Baillie, Amber L. Beitelshees, Yan Gong, Mohamed H A Shahin, Stephen T. Turner, Arlene Chapman, John G. Gums, Stephen H. Boyle, Hongjie Zhu, William R. Wikoff, Eric Boerwinkle, Oliver Fiehn, Reginald F. Frye, Rima Kaddurah-Daouk, Julie A. Johnson

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background-Circulating microRNAs (miRNAs) are emerging as novel disease biomarkers. We aimed to explore the association between circulating miRNAs and the occurrence of acute myocardial infarction (AMI) in Chinese populations. Methods and Results-In the discovery stage, the plasma of 20 patients with AMI and 20 controls were pooled respectively and profiled by massively parallel sequencing. Seventy-seven miRNAs showed differential expression. Selected miRNAs were validated in 178 patients with AMI and 198 controls using quantitative reverse transcriptase polymerase chain reaction assays and further replicated in 150 patients with AMI and 150 controls. Results suggest that miR-320b and miR-125b levels were significantly lower in patients with AMI than in controls in both validation populations (P>0.0001). Lower levels of miR-320b and miR-125b were associated with increased occurrence of AMI (adjusted odds ratio, 4.71; 95% confidence interval, 2.96-7.48 and odds ratio, 4.27; 95% confidence interval, 2.84-6.41, respectively). Addition of the 2 miRNAs to traditional risk factors led to a significant improvement in the area under the curve from 0.822 (95% confidence interval, 0.787-0.856) to 0.871 (95% confidence interval, 0.842- 0.900), with a net reclassification improvement of 20.45% (P>0.0001) and an integrated discrimination improvement of 0.16 (P>0.0001) for patients with AMI. A functional study showed that miR-320b and miR-125b could regulate the expression profiles of genes enriched in several signal transduction pathways critical for coronary heart disease in human vascular endothelial cells. Conclusions-The plasma levels of miR-320b and miR-125b were significantly lower in patients with AMI when compared with controls, and these miRNAs may be involved in the pathogenesis of coronary heart disease.

Original languageEnglish (US)
Pages (from-to)199-205
Number of pages7
JournalCirculation: Cardiovascular Genetics
Volume7
Issue number2
DOIs
StatePublished - 2014

Fingerprint

Fasting
Diabetes Mellitus
MicroRNAs
Myocardial Infarction
Amino Acids
Glucose
Confidence Intervals
Coronary Disease
Odds Ratio
High-Throughput Nucleotide Sequencing
Reverse Transcriptase Polymerase Chain Reaction
Transcriptome
Population
Area Under Curve
Signal Transduction
Endothelial Cells
Biomarkers

Keywords

  • Atherosclerosis
  • MicroRNAs
  • Myocardial infarction
  • Plasma

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)
  • Genetics

Cite this

Cooper-DeHoff, R. M., Hou, W., Weng, L., Baillie, R. A., Beitelshees, A. L., Gong, Y., ... Johnson, J. A. (2014). Is a diabetes mellitus-linked amino acid signature associated with β-blocker-induced impaired fasting glucose. Circulation: Cardiovascular Genetics, 7(2), 199-205. https://doi.org/10.1161/CIRCGENETICS.113.000294

Is a diabetes mellitus-linked amino acid signature associated with β-blocker-induced impaired fasting glucose. / Cooper-DeHoff, Rhonda M.; Hou, Wei; Weng, Liming; Baillie, Rebecca A.; Beitelshees, Amber L.; Gong, Yan; Shahin, Mohamed H A; Turner, Stephen T.; Chapman, Arlene; Gums, John G.; Boyle, Stephen H.; Zhu, Hongjie; Wikoff, William R.; Boerwinkle, Eric; Fiehn, Oliver; Frye, Reginald F.; Kaddurah-Daouk, Rima; Johnson, Julie A.

In: Circulation: Cardiovascular Genetics, Vol. 7, No. 2, 2014, p. 199-205.

Research output: Contribution to journalArticle

Cooper-DeHoff, RM, Hou, W, Weng, L, Baillie, RA, Beitelshees, AL, Gong, Y, Shahin, MHA, Turner, ST, Chapman, A, Gums, JG, Boyle, SH, Zhu, H, Wikoff, WR, Boerwinkle, E, Fiehn, O, Frye, RF, Kaddurah-Daouk, R & Johnson, JA 2014, 'Is a diabetes mellitus-linked amino acid signature associated with β-blocker-induced impaired fasting glucose', Circulation: Cardiovascular Genetics, vol. 7, no. 2, pp. 199-205. https://doi.org/10.1161/CIRCGENETICS.113.000294
Cooper-DeHoff, Rhonda M. ; Hou, Wei ; Weng, Liming ; Baillie, Rebecca A. ; Beitelshees, Amber L. ; Gong, Yan ; Shahin, Mohamed H A ; Turner, Stephen T. ; Chapman, Arlene ; Gums, John G. ; Boyle, Stephen H. ; Zhu, Hongjie ; Wikoff, William R. ; Boerwinkle, Eric ; Fiehn, Oliver ; Frye, Reginald F. ; Kaddurah-Daouk, Rima ; Johnson, Julie A. / Is a diabetes mellitus-linked amino acid signature associated with β-blocker-induced impaired fasting glucose. In: Circulation: Cardiovascular Genetics. 2014 ; Vol. 7, No. 2. pp. 199-205.
@article{b08e06a78b7a44e2b5730af3be32d21b,
title = "Is a diabetes mellitus-linked amino acid signature associated with β-blocker-induced impaired fasting glucose",
abstract = "Background-Circulating microRNAs (miRNAs) are emerging as novel disease biomarkers. We aimed to explore the association between circulating miRNAs and the occurrence of acute myocardial infarction (AMI) in Chinese populations. Methods and Results-In the discovery stage, the plasma of 20 patients with AMI and 20 controls were pooled respectively and profiled by massively parallel sequencing. Seventy-seven miRNAs showed differential expression. Selected miRNAs were validated in 178 patients with AMI and 198 controls using quantitative reverse transcriptase polymerase chain reaction assays and further replicated in 150 patients with AMI and 150 controls. Results suggest that miR-320b and miR-125b levels were significantly lower in patients with AMI than in controls in both validation populations (P>0.0001). Lower levels of miR-320b and miR-125b were associated with increased occurrence of AMI (adjusted odds ratio, 4.71; 95{\%} confidence interval, 2.96-7.48 and odds ratio, 4.27; 95{\%} confidence interval, 2.84-6.41, respectively). Addition of the 2 miRNAs to traditional risk factors led to a significant improvement in the area under the curve from 0.822 (95{\%} confidence interval, 0.787-0.856) to 0.871 (95{\%} confidence interval, 0.842- 0.900), with a net reclassification improvement of 20.45{\%} (P>0.0001) and an integrated discrimination improvement of 0.16 (P>0.0001) for patients with AMI. A functional study showed that miR-320b and miR-125b could regulate the expression profiles of genes enriched in several signal transduction pathways critical for coronary heart disease in human vascular endothelial cells. Conclusions-The plasma levels of miR-320b and miR-125b were significantly lower in patients with AMI when compared with controls, and these miRNAs may be involved in the pathogenesis of coronary heart disease.",
keywords = "Atherosclerosis, MicroRNAs, Myocardial infarction, Plasma",
author = "Cooper-DeHoff, {Rhonda M.} and Wei Hou and Liming Weng and Baillie, {Rebecca A.} and Beitelshees, {Amber L.} and Yan Gong and Shahin, {Mohamed H A} and Turner, {Stephen T.} and Arlene Chapman and Gums, {John G.} and Boyle, {Stephen H.} and Hongjie Zhu and Wikoff, {William R.} and Eric Boerwinkle and Oliver Fiehn and Frye, {Reginald F.} and Rima Kaddurah-Daouk and Johnson, {Julie A.}",
year = "2014",
doi = "10.1161/CIRCGENETICS.113.000294",
language = "English (US)",
volume = "7",
pages = "199--205",
journal = "Circulation. Genomic and precision medicine",
issn = "1942-325X",
publisher = "Lippincott Williams and Wilkins Ltd.",
number = "2",

}

TY - JOUR

T1 - Is a diabetes mellitus-linked amino acid signature associated with β-blocker-induced impaired fasting glucose

AU - Cooper-DeHoff, Rhonda M.

AU - Hou, Wei

AU - Weng, Liming

AU - Baillie, Rebecca A.

AU - Beitelshees, Amber L.

AU - Gong, Yan

AU - Shahin, Mohamed H A

AU - Turner, Stephen T.

AU - Chapman, Arlene

AU - Gums, John G.

AU - Boyle, Stephen H.

AU - Zhu, Hongjie

AU - Wikoff, William R.

AU - Boerwinkle, Eric

AU - Fiehn, Oliver

AU - Frye, Reginald F.

AU - Kaddurah-Daouk, Rima

AU - Johnson, Julie A.

PY - 2014

Y1 - 2014

N2 - Background-Circulating microRNAs (miRNAs) are emerging as novel disease biomarkers. We aimed to explore the association between circulating miRNAs and the occurrence of acute myocardial infarction (AMI) in Chinese populations. Methods and Results-In the discovery stage, the plasma of 20 patients with AMI and 20 controls were pooled respectively and profiled by massively parallel sequencing. Seventy-seven miRNAs showed differential expression. Selected miRNAs were validated in 178 patients with AMI and 198 controls using quantitative reverse transcriptase polymerase chain reaction assays and further replicated in 150 patients with AMI and 150 controls. Results suggest that miR-320b and miR-125b levels were significantly lower in patients with AMI than in controls in both validation populations (P>0.0001). Lower levels of miR-320b and miR-125b were associated with increased occurrence of AMI (adjusted odds ratio, 4.71; 95% confidence interval, 2.96-7.48 and odds ratio, 4.27; 95% confidence interval, 2.84-6.41, respectively). Addition of the 2 miRNAs to traditional risk factors led to a significant improvement in the area under the curve from 0.822 (95% confidence interval, 0.787-0.856) to 0.871 (95% confidence interval, 0.842- 0.900), with a net reclassification improvement of 20.45% (P>0.0001) and an integrated discrimination improvement of 0.16 (P>0.0001) for patients with AMI. A functional study showed that miR-320b and miR-125b could regulate the expression profiles of genes enriched in several signal transduction pathways critical for coronary heart disease in human vascular endothelial cells. Conclusions-The plasma levels of miR-320b and miR-125b were significantly lower in patients with AMI when compared with controls, and these miRNAs may be involved in the pathogenesis of coronary heart disease.

AB - Background-Circulating microRNAs (miRNAs) are emerging as novel disease biomarkers. We aimed to explore the association between circulating miRNAs and the occurrence of acute myocardial infarction (AMI) in Chinese populations. Methods and Results-In the discovery stage, the plasma of 20 patients with AMI and 20 controls were pooled respectively and profiled by massively parallel sequencing. Seventy-seven miRNAs showed differential expression. Selected miRNAs were validated in 178 patients with AMI and 198 controls using quantitative reverse transcriptase polymerase chain reaction assays and further replicated in 150 patients with AMI and 150 controls. Results suggest that miR-320b and miR-125b levels were significantly lower in patients with AMI than in controls in both validation populations (P>0.0001). Lower levels of miR-320b and miR-125b were associated with increased occurrence of AMI (adjusted odds ratio, 4.71; 95% confidence interval, 2.96-7.48 and odds ratio, 4.27; 95% confidence interval, 2.84-6.41, respectively). Addition of the 2 miRNAs to traditional risk factors led to a significant improvement in the area under the curve from 0.822 (95% confidence interval, 0.787-0.856) to 0.871 (95% confidence interval, 0.842- 0.900), with a net reclassification improvement of 20.45% (P>0.0001) and an integrated discrimination improvement of 0.16 (P>0.0001) for patients with AMI. A functional study showed that miR-320b and miR-125b could regulate the expression profiles of genes enriched in several signal transduction pathways critical for coronary heart disease in human vascular endothelial cells. Conclusions-The plasma levels of miR-320b and miR-125b were significantly lower in patients with AMI when compared with controls, and these miRNAs may be involved in the pathogenesis of coronary heart disease.

KW - Atherosclerosis

KW - MicroRNAs

KW - Myocardial infarction

KW - Plasma

UR - http://www.scopus.com/inward/record.url?scp=84903603874&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84903603874&partnerID=8YFLogxK

U2 - 10.1161/CIRCGENETICS.113.000294

DO - 10.1161/CIRCGENETICS.113.000294

M3 - Article

C2 - 24627569

AN - SCOPUS:84903603874

VL - 7

SP - 199

EP - 205

JO - Circulation. Genomic and precision medicine

JF - Circulation. Genomic and precision medicine

SN - 1942-325X

IS - 2

ER -