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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:2149.)
© 2004 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Differential Gene Expression of Blood-Derived Cell Lines in Familial Combined Hyperlipidemia

Fulvio Morello; Tjerk W.A. de Bruin; Jerome I. Rotter; Richard E. Pratt; Carla J.H. van der Kallen; Gary A. Hladik; Victor J. Dzau; Choong-Chin Liew; Yii-Der I. Chen

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 Department of Medicine (T.W.A.d.B., C.J.H.v.d.K.), Cardiovascular Research Institute Maastricht, Maastricht, the Netherlands; and the Medical Genetics Institute (J.I.R., G.A.H.) and the Department of Medicine and Obstetrics/Gynecology (Y.-D.I.C.), Cedars-Sinai Research Institute, Los Angeles, Calif.

Correspondence to Choong-Chin Liew, HMS New Research Building, 77 Avenue Louis Pasteur Avenue, Boston, MA 02115. E-mail cliew{at}rics.bwh.harvard.edu

Objectives— The genetic background of familial combined hyperlipidemia (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.

We studied the transcriptional profile of FCHL-derived lymphoblast cell lines using microarrays. Of note was the differential expression of EGR-1, several lipid metabolism-related genes, and many novel genes.

Key Words: dyslipidemia • blood cells • microarray • genomics • genetics

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