Serum Proteomics in African American Female Patients with Irritable Bowel Syndrome: An Exploratory Study

Kristen R. Weaver; Gail D.Eramo Melkus; Jason Fletcher; Wendy A. Henderson

doi:10.1097/NNR.0000000000000281

Serum Proteomics in African American Female Patients with Irritable Bowel Syndrome: An Exploratory Study

Kristen R. Weaver, Gail D.Eramo Melkus, Jason Fletcher, Wendy A. Henderson

Nursing

Research output: Contribution to journal › Article › peer-review

Abstract

Background Sex and subtype differences within patients with irritable bowel syndrome (IBS) complicate the understanding of disorder pathogenesis and hinder the design of efficacious, therapeutic interventions. Objectives The aims of this study were to harness the power of shotgun proteomic analysis, identify circulating proteins that differentiate African American female patients with IBS from healthy controls (HC), and gain biological insight on symptomatology. Methods Serum proteome analysis was performed upon a cohort of overweight, African American female participants with constipation predominant IBS symptoms (n = 5) and HC (n = 5), matched on age, sex, years of education, body mass index, and 11 physiological markers. Tandem mass tags for multiplexed proteomic analysis were performed, incorporating reverse-phase liquid chromatography and liquid chromatography-tandem mass spectrometry. Results Participants with IBS did not differ from HC in demographics, clinical characteristics, or initial proteomic analysis. Nested case control analysis of six samples (IBS: n = 3, HC: n = 3), hierarchically clustered into two main groups, with 12 out of 1,317 proteins significantly different in levels of expression: TGFβ1, PF4V1, PF4, APP, MMP9, PPBP, CTGF, SRGN, THBS1, WRN, LTBP1 (Isoform 3), and IGLV5-48. Top associations of identified proteins in DAVID and STRING resources (upregulated in HC vs. IBS) involve platelet alpha granule lumen, platelet activation/degranulation, extracellular region, and secretion by cell. Discussion Differentially expressed proteins between participants with IBS and HC involving platelet-related associations prompt inquiry as to differences in serotonergic signaling, inflammatory or immunomodulatory mechanisms underlying IBS symptomatology. Although preliminary and requiring validation in larger cohorts, these findings bear relevance to understanding pathogenic processes of IBS and biological effects of the disorder.

Original language	English (US)
Pages (from-to)	261-267
Number of pages	7
Journal	Nursing research
Volume	67
Issue number	3
DOIs	https://doi.org/10.1097/NNR.0000000000000281
State	Published - May 1 2018

Keywords

IBS-C
TGFB1
irritable bowel syndrome
platelet-associated proteins
proteomics

ASJC Scopus subject areas

Medicine(all)

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10.1097/NNR.0000000000000281

Cite this

@article{0ac93248502344c6b027b207bb6b225d,

title = "Serum Proteomics in African American Female Patients with Irritable Bowel Syndrome: An Exploratory Study",

abstract = "Background Sex and subtype differences within patients with irritable bowel syndrome (IBS) complicate the understanding of disorder pathogenesis and hinder the design of efficacious, therapeutic interventions. Objectives The aims of this study were to harness the power of shotgun proteomic analysis, identify circulating proteins that differentiate African American female patients with IBS from healthy controls (HC), and gain biological insight on symptomatology. Methods Serum proteome analysis was performed upon a cohort of overweight, African American female participants with constipation predominant IBS symptoms (n = 5) and HC (n = 5), matched on age, sex, years of education, body mass index, and 11 physiological markers. Tandem mass tags for multiplexed proteomic analysis were performed, incorporating reverse-phase liquid chromatography and liquid chromatography-tandem mass spectrometry. Results Participants with IBS did not differ from HC in demographics, clinical characteristics, or initial proteomic analysis. Nested case control analysis of six samples (IBS: n = 3, HC: n = 3), hierarchically clustered into two main groups, with 12 out of 1,317 proteins significantly different in levels of expression: TGFβ1, PF4V1, PF4, APP, MMP9, PPBP, CTGF, SRGN, THBS1, WRN, LTBP1 (Isoform 3), and IGLV5-48. Top associations of identified proteins in DAVID and STRING resources (upregulated in HC vs. IBS) involve platelet alpha granule lumen, platelet activation/degranulation, extracellular region, and secretion by cell. Discussion Differentially expressed proteins between participants with IBS and HC involving platelet-related associations prompt inquiry as to differences in serotonergic signaling, inflammatory or immunomodulatory mechanisms underlying IBS symptomatology. Although preliminary and requiring validation in larger cohorts, these findings bear relevance to understanding pathogenic processes of IBS and biological effects of the disorder.",

keywords = "IBS-C, TGFB1, irritable bowel syndrome, platelet-associated proteins, proteomics",

author = "Weaver, {Kristen R.} and Melkus, {Gail D.Eramo} and Jason Fletcher and Henderson, {Wendy A.}",

note = "Funding Information: Accepted for publication January 21 2018. This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Nursing Research (KRW: Intramural Research Training Award, Graduate Partnership Program; WAH: 1ZIANR000018-01-08). Further support was provided to K. R. W. by the Heilbrunn Family Center for Research Nursing of The Rockefeller University and by the Jonas Center for Nursing and Veterans Healthcare. This work was presented at the European Society of Neurogastroenterology and Motility NeuroGASTRO 2017 Conference, and the abstract was published in a Special Issue of Neurogastroenterology and Motility (August 2017, Volume 29, Issue Supplement S2). The authors would like to acknowledge Dr. Marjan Gucek and Dr. Yanling Yang of the Proteomics Core, Division of Intramural Research, National Heart, Lung, and Blood Institute, for performing proteomic research and data analysis. The authors declare no conflicts of interest. Ethical Conduct of Research: This investigation was performed as a sub-study of a larger investigation, which has received institutional review board approval from the National Institutes of Health (Protocol 09-NR-0064). Clinical Trial Registration: This study was a substudy of a larger investigation, which registered on ClinicalTrial.gov (NCT00824941). The first participant was enrolled in February, 2009. Corresponding author: Kristen R. Weaver, PhD, CRNP, National Institute of Nursing Research, National Institutes of Health, 10 Center Drive, Room 2-2339, Bethesda, MD 20892 (e-mail: kweave22@jhmi.edu). Publisher Copyright: {\textcopyright} 2018 Wolters Kluwer Health, Inc. All rights reserved.",

year = "2018",

month = may,

day = "1",

doi = "10.1097/NNR.0000000000000281",

language = "English (US)",

volume = "67",

pages = "261--267",

journal = "Nursing Research",

issn = "0029-6562",

publisher = "Lippincott Williams and Wilkins",

number = "3",

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TY - JOUR

T1 - Serum Proteomics in African American Female Patients with Irritable Bowel Syndrome

T2 - An Exploratory Study

AU - Weaver, Kristen R.

AU - Melkus, Gail D.Eramo

AU - Fletcher, Jason

AU - Henderson, Wendy A.

N1 - Funding Information: Accepted for publication January 21 2018. This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Nursing Research (KRW: Intramural Research Training Award, Graduate Partnership Program; WAH: 1ZIANR000018-01-08). Further support was provided to K. R. W. by the Heilbrunn Family Center for Research Nursing of The Rockefeller University and by the Jonas Center for Nursing and Veterans Healthcare. This work was presented at the European Society of Neurogastroenterology and Motility NeuroGASTRO 2017 Conference, and the abstract was published in a Special Issue of Neurogastroenterology and Motility (August 2017, Volume 29, Issue Supplement S2). The authors would like to acknowledge Dr. Marjan Gucek and Dr. Yanling Yang of the Proteomics Core, Division of Intramural Research, National Heart, Lung, and Blood Institute, for performing proteomic research and data analysis. The authors declare no conflicts of interest. Ethical Conduct of Research: This investigation was performed as a sub-study of a larger investigation, which has received institutional review board approval from the National Institutes of Health (Protocol 09-NR-0064). Clinical Trial Registration: This study was a substudy of a larger investigation, which registered on ClinicalTrial.gov (NCT00824941). The first participant was enrolled in February, 2009. Corresponding author: Kristen R. Weaver, PhD, CRNP, National Institute of Nursing Research, National Institutes of Health, 10 Center Drive, Room 2-2339, Bethesda, MD 20892 (e-mail: kweave22@jhmi.edu). Publisher Copyright: © 2018 Wolters Kluwer Health, Inc. All rights reserved.

PY - 2018/5/1

Y1 - 2018/5/1

N2 - Background Sex and subtype differences within patients with irritable bowel syndrome (IBS) complicate the understanding of disorder pathogenesis and hinder the design of efficacious, therapeutic interventions. Objectives The aims of this study were to harness the power of shotgun proteomic analysis, identify circulating proteins that differentiate African American female patients with IBS from healthy controls (HC), and gain biological insight on symptomatology. Methods Serum proteome analysis was performed upon a cohort of overweight, African American female participants with constipation predominant IBS symptoms (n = 5) and HC (n = 5), matched on age, sex, years of education, body mass index, and 11 physiological markers. Tandem mass tags for multiplexed proteomic analysis were performed, incorporating reverse-phase liquid chromatography and liquid chromatography-tandem mass spectrometry. Results Participants with IBS did not differ from HC in demographics, clinical characteristics, or initial proteomic analysis. Nested case control analysis of six samples (IBS: n = 3, HC: n = 3), hierarchically clustered into two main groups, with 12 out of 1,317 proteins significantly different in levels of expression: TGFβ1, PF4V1, PF4, APP, MMP9, PPBP, CTGF, SRGN, THBS1, WRN, LTBP1 (Isoform 3), and IGLV5-48. Top associations of identified proteins in DAVID and STRING resources (upregulated in HC vs. IBS) involve platelet alpha granule lumen, platelet activation/degranulation, extracellular region, and secretion by cell. Discussion Differentially expressed proteins between participants with IBS and HC involving platelet-related associations prompt inquiry as to differences in serotonergic signaling, inflammatory or immunomodulatory mechanisms underlying IBS symptomatology. Although preliminary and requiring validation in larger cohorts, these findings bear relevance to understanding pathogenic processes of IBS and biological effects of the disorder.

AB - Background Sex and subtype differences within patients with irritable bowel syndrome (IBS) complicate the understanding of disorder pathogenesis and hinder the design of efficacious, therapeutic interventions. Objectives The aims of this study were to harness the power of shotgun proteomic analysis, identify circulating proteins that differentiate African American female patients with IBS from healthy controls (HC), and gain biological insight on symptomatology. Methods Serum proteome analysis was performed upon a cohort of overweight, African American female participants with constipation predominant IBS symptoms (n = 5) and HC (n = 5), matched on age, sex, years of education, body mass index, and 11 physiological markers. Tandem mass tags for multiplexed proteomic analysis were performed, incorporating reverse-phase liquid chromatography and liquid chromatography-tandem mass spectrometry. Results Participants with IBS did not differ from HC in demographics, clinical characteristics, or initial proteomic analysis. Nested case control analysis of six samples (IBS: n = 3, HC: n = 3), hierarchically clustered into two main groups, with 12 out of 1,317 proteins significantly different in levels of expression: TGFβ1, PF4V1, PF4, APP, MMP9, PPBP, CTGF, SRGN, THBS1, WRN, LTBP1 (Isoform 3), and IGLV5-48. Top associations of identified proteins in DAVID and STRING resources (upregulated in HC vs. IBS) involve platelet alpha granule lumen, platelet activation/degranulation, extracellular region, and secretion by cell. Discussion Differentially expressed proteins between participants with IBS and HC involving platelet-related associations prompt inquiry as to differences in serotonergic signaling, inflammatory or immunomodulatory mechanisms underlying IBS symptomatology. Although preliminary and requiring validation in larger cohorts, these findings bear relevance to understanding pathogenic processes of IBS and biological effects of the disorder.

KW - IBS-C

KW - TGFB1

KW - irritable bowel syndrome

KW - platelet-associated proteins

KW - proteomics

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JO - Nursing Research

JF - Nursing Research

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ER -

Serum Proteomics in African American Female Patients with Irritable Bowel Syndrome: An Exploratory Study

Abstract

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