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PMID: 21368773 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Peripheral blood gene expression profiles in metabolic syndrome, coronary artery disease and type 2 diabetes.

Genes and immunity ·Vol. 12 ·No. 5 ·2011-07-00 ·Pages 341-51

Grayson BL, Wang L, Aune TM

Abstract

To determine if individuals with metabolic disorders possess unique gene expression profiles, we compared transcript levels in peripheral blood from patients with coronary artery disease (CAD), type 2 diabetes (T2D) and their precursor state, metabolic syndrome to those of control (CTRL) subjects and subjects with rheumatoid arthritis (RA). The gene expression profile of each metabolic state was distinguishable from CTRLs and correlated with other metabolic states more than with RA. Of note, subjects in the metabolic cohorts overexpressed gene sets that participate in the innate immune response. Genes involved in activation of the pro-inflammatory transcription factor, NF-κB, were overexpressed in CAD whereas genes differentially expressed in T2D have key roles in T-cell activation and signaling. Reverse transcriptase PCR validation confirmed microarray results. Furthermore, several genes differentially expressed in human metabolic disorders have been previously shown to participate in inflammatory responses in murine models of obesity and T2D. Taken together, these data demonstrate that peripheral blood from individuals with metabolic disorders display overlapping and non-overlapping patterns of gene expression indicative of unique, underlying immune processes.

MeSH Terms
Arthritis, Rheumatoid/genetics Cluster Analysis Coronary Artery Disease/genetics Diabetes Mellitus, Type 2/genetics Gene Expression Profiling Gene Expression Regulation Genetic Predisposition to Disease/genetics Humans Metabolic Syndrome/genetics Polymorphism, Single Nucleotide/genetics Reproducibility of Results
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Grayson B L
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Wang L
Aune T M
References (47)
47 references, click to expand
  1. Noninvasive diagnostic and prognostic assessment of individuals with suspected coronary artery disease: coronary computed tomographic angiography perspective.
    Circ Cardiovasc Imaging. 2008 Nov;1(3):270-81; discussion 281 PMID: 19808551
  2. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium.
    Nat Genet. 2000 May;25(1):25-9 PMID: 10802651
  3. TM4: a free, open-source system for microarray data management and analysis.
    Biotechniques. 2003 Feb;34(2):374-8 PMID: 12613259
  4. Rheumatoid arthritis.
    Lancet. 2009 Feb 21;373(9664):659-72 PMID: 19157532
  5. The pathogenesis of atherosclerosis: a perspective for the 1990s.
    Nature. 1993 Apr 29;362(6423):801-9 PMID: 8479518
  6. Bioconductor: an open source framework for bioinformatics and computational biology.
    Methods Enzymol. 2006;411:119-34 PMID: 16939789
  7. Type 2 diabetes: principles of pathogenesis and therapy.
    Lancet. 2005 Apr 9-15;365(9467):1333-46 PMID: 15823385
  8. Can metabolic syndrome usefully predict cardiovascular disease and diabetes? Outcome data from two prospective studies.
    Lancet. 2008 Jun 7;371(9628):1927-35 PMID: 18501419
  9. Gene expression profiles in human autoimmune disease.
    Curr Pharm Des. 2003;9(23):1905-17 PMID: 12871194
  10. Complex nature of SNP genotype effects on gene expression in primary human leucocytes.
    BMC Med Genomics. 2009 Jan 07;2:1 PMID: 19128478
  11. Identification of gene expression signatures in autoimmune disease without the influence of familial resemblance.
    Hum Mol Genet. 2006 Feb 1;15(3):501-9 PMID: 16371420
  12. Global and societal implications of the diabetes epidemic.
    Nature. 2001 Dec 13;414(6865):782-7 PMID: 11742409
  13. Gene Expression Omnibus: NCBI gene expression and hybridization array data repository.
    Nucleic Acids Res. 2002 Jan 1;30(1):207-10 PMID: 11752295
  14. Body mass index, metabolic syndrome, and risk of type 2 diabetes or cardiovascular disease.
    J Clin Endocrinol Metab. 2006 Aug;91(8):2906-12 PMID: 16735483
  15. Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus.
    Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2610-5 PMID: 12604793
  16. Gene expression profile in multiple sclerosis patients and healthy controls: identifying pathways relevant to disease.
    Hum Mol Genet. 2003 Sep 1;12(17):2191-9 PMID: 12915464
  17. The metabolic syndrome--a new worldwide definition.
    Lancet. 2005 Sep 24-30;366(9491):1059-62 PMID: 16182882
  18. Metabolic syndrome and risk of incident cardiovascular events and death: a systematic review and meta-analysis of longitudinal studies.
    J Am Coll Cardiol. 2007 Jan 30;49(4):403-14 PMID: 17258085
  19. Potential etiologic and functional implications of genome-wide association loci for human diseases and traits.
    Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9362-7 PMID: 19474294
  20. CXCL14 and insulin action.
    Vitam Horm. 2009;80:107-23 PMID: 19251036
  21. Differential and correlation analyses of microarray gene expression data in the CEPH Utah families.
    Genomics. 2008 Aug;92(2):94-100 PMID: 18519161
  22. Prevalence of the metabolic syndrome defined by the International Diabetes Federation among adults in the U.S.
    Diabetes Care. 2005 Nov;28(11):2745-9 PMID: 16249550
  23. CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity.
    Nat Med. 2009 Aug;15(8):914-20 PMID: 19633658
  24. Atherosclerosis: basic mechanisms. Oxidation, inflammation, and genetics.
    Circulation. 1995 May 1;91(9):2488-96 PMID: 7729036
  25. TLR4 links innate immunity and fatty acid-induced insulin resistance.
    J Clin Invest. 2006 Nov;116(11):3015-25 PMID: 17053832
  26. An integrated approach for the analysis of biological pathways using mixed models.
    PLoS Genet. 2008 Jul;4(7):e1000115 PMID: 18852846
  27. Pathway analysis of seven common diseases assessed by genome-wide association.
    Genomics. 2008 Nov;92(5):265-72 PMID: 18722519
  28. Metabolic syndrome and risk of cardiovascular disease: a meta-analysis.
    Am J Med. 2006 Oct;119(10):812-9 PMID: 17000207
  29. Obesity-induced inflammatory changes in adipose tissue.
    J Clin Invest. 2003 Dec;112(12):1785-8 PMID: 14679172
  30. Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization: new molecules and patterns of gene expression.
    J Immunol. 2006 Nov 15;177(10):7303-11 PMID: 17082649
  31. Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment.
    N Engl J Med. 2004 Aug 5;351(6):533-42 PMID: 15295046
  32. Tolerization of dendritic cells by T(S) cells: the crucial role of inhibitory receptors ILT3 and ILT4.
    Nat Immunol. 2002 Mar;3(3):237-43 PMID: 11875462
  33. Reduced p53 in peripheral blood mononuclear cells from patients with rheumatoid arthritis is associated with loss of radiation-induced apoptosis.
    Arthritis Rheum. 2005 Apr;52(4):1047-57 PMID: 15818671
  34. Cytoscape: a software environment for integrated models of biomolecular interaction networks.
    Genome Res. 2003 Nov;13(11):2498-504 PMID: 14597658
  35. Heart disease and stroke statistics--2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee.
    Circulation. 2009 Jan 27;119(3):e21-181 PMID: 19075105
  36. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis.
    Arthritis Rheum. 1988 Mar;31(3):315-24 PMID: 3358796
  37. Cardiac adiposity and global cardiometabolic risk: new concept and clinical implication.
    Circ J. 2009 Jan;73(1):27-34 PMID: 19057089
  38. Gene expression profiling in the adult Down syndrome brain.
    Genomics. 2007 Dec;90(6):647-60 PMID: 17950572
  39. Interleukin 4 receptor is associated with an increase in body mass index in Koreans.
    Life Sci. 2008 May 7;82(19-20):1040-3 PMID: 18433792
  40. Metabolic syndrome and incident diabetes: current state of the evidence.
    Diabetes Care. 2008 Sep;31(9):1898-904 PMID: 18591398
  41. The metabolic syndrome.
    Lancet. 2005 Apr 16-22;365(9468):1415-28 PMID: 15836891
  42. A model of insulin resistance in mice, born to diabetic pregnancy, is associated with alterations of transcription-related genes in pancreas and epididymal adipose tissue.
    J Obes. 2011;2011: PMID: 20936114
  43. A unified mixed effects model for gene set analysis of time course microarray experiments.
    Stat Appl Genet Mol Biol. 2009;8:Article 47 PMID: 19954419
  44. Gene-expression signatures in breast cancer.
    N Engl J Med. 2009 Feb 19;360(8):790-800 PMID: 19228622
  45. Treatment-specific changes in gene expression discriminate in vivo drug response in human leukemia cells.
    Nat Genet. 2003 May;34(1):85-90 PMID: 12704389
  46. Shared gene expression profiles in individuals with autoimmune disease and unaffected first-degree relatives of individuals with autoimmune disease.
    Hum Mol Genet. 2005 May 15;14(10):1305-14 PMID: 15814587
  47. Gene expression changes in children with autism.
    Genomics. 2008 Jan;91(1):22-9 PMID: 18006270
Article Info
Journal
Genes and immunity
Abbr.
Genes Immun
ISSN
1476-5470
Published
2011-07-00
Epub
2011-00-03
Pages
341-51
Language
English
Region
England
NLM ID
100953417
PMCID
PMC3137736
Subset
IM
Grants
NIDDK NIH HHS · R42 DK065388 · United States
NIDDK NIH HHS · T32 DK07563 · United States
NIGMS NIH HHS · T32 GM07347 · United States
NCRR NIH HHS · TL1 RR024978 · United States
NIAID NIH HHS · R42 AI053984 · United States
NIAID NIH HHS · R42 AI053984-06 · United States
NIGMS NIH HHS · T32 GM007347 · United States
NIDDK NIH HHS · R42 DK065388-03 · United States
NIDDK NIH HHS · T32 DK007563 · United States
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