title: Differentially expressed genes in human peripheral blood as potential markers for statin response.
abstract: There is a considerable inter-individual variation in response to statin therapy and one third of patients do not meet their treatment goals. We aimed to identify differentially expressed genes that might be involved in the effects of statin treatment and to suggest potential markers to guide statin therapy. Forty-six healthy Korean subjects received atorvastatin; their whole-genome expression profiles in peripheral blood were analyzed before and after atorvastatin administration in relation with changes in lipid profiles. The expression patterns of the differentially expressed genes were also compared with the data of familial hypercholesterolemia (FH) patients and controls. Pairwise comparison analyses revealed differentially expressed genes involved in diverse biological processes and molecular functions related with immune responses. Atorvastain mainly affected antigen binding, immune or inflammatory response including interleukin pathways. Similar expression patterns of the genes were observed in patients with FH and controls. The Charcol-Leyden crystal (CLC), CCR2, CX3CR1, LRRN3, FOS, LDLR, HLA-DRB1, ERMN, and TCN1 genes were significantly associated with cholesterol levels or statin response. Interestingly, the CLC gene, which was significantly altered by atorvastatin administration and differentially expressed between FH patients and controls, showed much bigger change in high-responsive group than in low-responsive group. We identified differentially expressed genes that might be involved in mechanisms underlying the known pleiotropic effects of atorvastatin, baseline cholesterol levels, and drug response. Our findings suggest CLC as a new candidate marker for statin response, and further validation is needed.
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Seoul 135-710, South Korea.
authors.forename: Hong-Hee
authors.initials: HH
authors.lastname: Won
authors.forename: Suk Ran
authors.initials: SR
authors.lastname: Kim
authors.forename: Oh Young
authors.initials: OY
authors.lastname: Bang
authors.forename: Sang-Chol
authors.initials: SC
authors.lastname: Lee
authors.forename: Wooseong
authors.initials: W
authors.lastname: Huh
authors.forename: Jae-Wook
authors.initials: JW
authors.lastname: Ko
authors.forename: Hyung-Gun
authors.initials: HG
authors.lastname: Kim
authors.forename: Howard L
authors.initials: HL
authors.lastname: McLeod
authors.forename: Thomas M
authors.initials: TM
authors.lastname: O'Connell
authors.forename: Jong-Won
authors.initials: JW
authors.lastname: Kim
authors.forename: Soo-Youn
authors.initials: SY
authors.lastname: Lee
mesh_terms: D000328:Adult; D000069059:Atorvastatin; D054316:Biomarkers, Pharmacological / Q000097:blood; D002784:Cholesterol / Q000097:blood*; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling / Q000379:methods; D005802:Genes, MHC Class II / Q000187:drug effects; D015894:Genome, Human; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood* / Q000235:genetics; D008297:Male; D011758:Pyrroles / Q000008:administration & dosage*
chemical_list: D054316:Biomarkers, Pharmacological; D006538:Heptanoic Acids; D011758:Pyrroles; D002784:Cholesterol; D000069059:Atorvastatin