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 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.


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.
Freedman
Jane E
JE
Department of Medicine, Boston University School of Medicine, Whitaker Cardiovascular Institute, 700 Albany St, W-507, Boston, MA 02118, USA. freedmaj@bu.edu
Larson
Martin G
MG
Tanriverdi
Kahraman
K
O'Donnell
Christopher J
CJ
Morin
Kristine
K
Hakanson
Amanda S
AS
Vasan
Ramachandran S
RS
Johnson
Andrew D
AD
Iafrati
Mark D
MD
Benjamin
Emelia J
EJ
D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000378:metabolism* / Q000473:pathology; D015992:Body Mass Index; D015331:Cohort Studies; D003327:Coronary Disease / Q000097:blood* / Q000473:pathology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D018836:Inflammation Mediators / Q000378:metabolism*; D007962:Leukocytes / Q000378:metabolism* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000097:blood*; D012307:Risk Factors
D015415:Biomarkers; D018836:Inflammation Mediators; D012333:RNA, Messenger