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. 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.
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. 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.
Authors: Robert A Philibert; Steven R H Beach; Tracy D Gunter; Gene H Brody; Anup Madan; Meg Gerrard Journal: Am J Med Genet B Neuropsychiatr Genet Date: 2010-03-05 Impact factor: 3.568
Authors: Jeremy C Collette; Xiao-Ning Chen; Debra L Mills; Albert M Galaburda; Allan L Reiss; Ursula Bellugi; Julie R Korenberg Journal: J Hum Genet Date: 2009-03-13 Impact factor: 3.172
Authors: Marisa W Medina; Frederick Bauzon; Devesh Naidoo; Elizabeth Theusch; Kristen Stevens; Jessica Schilde; Christian Schubert; Lara M Mangravite; Lawrence L Rudel; Ryan E Temel; Heiko Runz; Ronald M Krauss Journal: Arterioscler Thromb Vasc Biol Date: 2014-07-17 Impact factor: 8.311