on September 23, 2004
Published online before print September 23, 2004, doi: 10.1161/01.ATV.0000145978.70872.63
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Submitted on April 28, 2004
Accepted on September 13, 2004
Differential Gene Expression of Blood-Derived Cell Lines in Familial Combined Hyperlipemia
Fulvio Morello ;
From the Department of Medicine (F.M., R.E.P., V.J.D., C.-C.L.), Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass; the Division of Medical Genetics (J.I.R., G.A.H., Y.-D.I.C.), Cedars-Sinai Research Institute, Los Angeles, Calif; and the Department of Medicine (T.W.A.d.B., C.J.H.v.d.K.), Cardiovascular Research Institute Maastricht, Maastricht, the Netherlands.
* To whom correspondence should be addressed. E-mail: cliew{at}rics.bwh.harvard.edu.
Objectives--The genetic background of familial combined hyperlipemia (FCHL) is currently unclear. We propose transcriptional profiling as a complementary tool for its understanding. Two hypotheses were tested: the existence of a disease-specific modification of gene expression in FCHL and the detectability of such a transcriptional profile in blood derived cell lines.
Methods and Results--We established lymphoblastic cell lines from FCHL patients and controls. The cells were cultured in fixed conditions and their basal expression profile was compared using microarrays; 166 genes were differentially expressed in FCHL-derived cell lines compared with controls, with enrichment in metabolism-related genes. Of note was the upregulation of EGR-1, previously found to be upregulated in the adipose tissue of FCHL patients, the upregulation of DCHR-7, the downregulation of LYPLA2, and the differential expression of several genes previously unrelated to FCHL. A cluster of potential EGR-1-regulated transcripts was also differentially expressed in FCHL cells.
Conclusion--Our data indicate that in FCHL, a disease-specific transcription profile is detectable in immortalized cell lines easily obtained from peripheral blood and provide complementary information to classical genetic approaches to FCHL and/or the metabolic syndrome.
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