Relation of platelet and leukocyte inflammatory transcripts to body mass index in the Framingham heart study.
Background: Although many genetic epidemiology and biomarker studies have been conducted to examine associations of genetic variants and circulating proteins with cardiovascular disease and risk factors, there has been little study of gene expression or transcriptomics. Quantitative differences in t...
| Publicado en: | Circulation Vol. 122; no. 2; pp. 119 - 130 |
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| Autores principales: | , , , , , , , , , , , , , , , , , , , |
| Formato: | research Journal Article |
| Publicado: |
Lippincott Williams & Wilkins
7/13/2010
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=105052439&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 105052439 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00097322 1FV jtl: Circulation issn: 00097322 maglogo: N pubinfo: dt: 7/13/2010 vid: 122 iid: 2 pid: 433 pub: Lippincott Williams & Wilkins place: Baltimore, Maryland artinfo: ui: 105052439 NLM20606121 2010712345 10.1161/CIRCULATIONAHA.109.928192 NLM20606121 PMC2910759 105052439 ppf: 119 ppct: 11 formats: tig: atl: Relation of platelet and leukocyte inflammatory transcripts to body mass index in the Framingham heart study. aug: au: Freedman JE Larson MG Tanriverdi K O'Donnell CJ Morin K Hakanson AS Vasan RS Johnson AD Iafrati MD Benjamin EJ Freedman, Jane E Larson, Martin G Tanriverdi, Kahraman O'Donnell, Christopher J Morin, Kristine Hakanson, Amanda S Vasan, Ramachandran S Johnson, Andrew D Iafrati, Mark D Benjamin, Emelia J affil: Department of Medicine, Boston University School of Medicine, Whitaker Cardiovascular Institute, 700 Albany St, W-507, Boston, MA 02118, USA sug: subj: Blood Platelets Metabolism Body Mass Index Coronary Disease Blood Genes Inflammation Mediators Metabolism Leukocytes Metabolism RNA Blood Biochips Biological Markers Blood Blood Platelets Pathology Coronary Disease Pathology Genetic Techniques Leukocytes Pathology Prospective Studies Risk Factors ab: Background: Although many genetic epidemiology and biomarker studies have been conducted to examine associations of genetic variants and circulating proteins with cardiovascular disease and risk factors, there has been little study of gene expression or transcriptomics. Quantitative differences in the abundance of transcripts has been demonstrated in malignancies, but gene expression from a large community-based cohort examining risk of cardiovascular disease has never been reported.Methods and Results: On the basis of preliminary microarray data and previously suggested genes from the literature, we measured expression of 48 genes by high-throughput quantitative reverse-transcriptase polymerase chain reaction in 1846 participants of the Framingham Offspring cohort from RNA derived from isolated platelets and leukocytes. A multivariable stepwise regression model was used to assess clinical correlates of quantitative RNA expression. For specific inflammatory platelet-derived transcripts, including ICAM1, IFNG, IL1R1, IL6, MPO, COX2, TNF, TLR2, and TLR4, there were significant associations with higher body mass index (BMI). Compared with platelets, fewer leukocyte-derived transcripts were associated with BMI or other cardiovascular risk factors. Select transcripts were found to be highly heritable, including GPIBA and COX1. Almost uniformly, heritable transcripts were not those associated with BMI.Conclusions: Inflammatory transcripts derived from platelets, particularly those part of the nuclear factor kappa B pathway, are associated with BMI, whereas others are heritable. This is the first study, using a large community-based cohort, to demonstrate clinical correlates of gene expression and is consistent with the hypothesis that specific peripheral-blood transcripts play a role in the pathogenesis of coronary heart disease and its risk factors. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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