Differential gene expression of blood-derived cell lines in familial combined hyperlipidemia.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Morello
Fulvio
F
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass, USA.
de Bruin
Tjerk W A
TW
Rotter
Jerome I
JI
Pratt
Richard E
RE
van der Kallen
Carla J H
CJ
Hladik
Gary A
GA
Dzau
Victor J
VJ
Liew
Choong-Chin
CC
Chen
Yii-Der I
YD
D002478:Cells, Cultured; D016000:Cluster Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D051766:Early Growth Response Protein 1; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods* / Q000706:statistics & numerical data; D005786:Gene Expression Regulation / Q000235:genetics; D005796:Genes / Q000235:genetics; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000235:genetics* / Q000473:pathology; D017874:Immediate-Early Proteins / Q000235:genetics; D008214:Lymphocytes / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods* / Q000706:statistics & numerical data; D012313:RNA / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014157:Transcription Factors / Q000235:genetics
D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D014157:Transcription Factors; D012313:RNA