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Differentially expressed genes in human peripheral blood as potential markers for statin response

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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.

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Acknowledgments

This work was supported by the Samsung Biomedical Research Institute grant, #SBRI C-B0-228-1; a grant from the Korean Ministry of Education, Science and Technology, (FPR08A2-130) of the 21C Frontier Functional Proteomics Program; and a grant from the Korea Healthcare technology R&D Project, Ministry of Health & Welfare, Republic of Korea (A070001).

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Authors and Affiliations

  1. Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, 135-710, South Korea

    Hong-Hee Won

  2. Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon, 305-701, South Korea

    Hong-Hee Won

  3. Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul, 135-710, South Korea

    Suk Ran Kim, Jong-Won Kim & Soo-Youn Lee

  4. Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 135-710, South Korea

    Oh Young Bang

  5. Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 135-710, South Korea

    Sang-Chol Lee & Wooseong Huh

  6. Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Seoul, 135-710, South Korea

    Wooseong Huh, Jae-Wook Ko & Soo-Youn Lee

  7. Department of Pharmacology, College of Medicine, Dankook University, Chonan, 330-715, South Korea

    Hyung-Gun Kim

  8. UNC Institute for Pharmacogenomics and Individualized Therapy, University of North Carolina, Chapel Hill, NC, 27599, USA

    Howard L. McLeod

  9. Division of Pharmacotherapy and Experimental Therapeutics, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA

    Thomas M. O’Connell

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  1. Hong-Hee Won
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Correspondence to Soo-Youn Lee.

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Supplementary Table 1

Differentially expressed genes between the high LDL group (n = 10) and the low LDL group (n = 10; XLS 39 kb)

Supplementary Table 2

Univariate linear regression analyses for the subjects with LDL decrease > 5% at 48 h (n = 29; XLS 19 kb)

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Won, HH., Kim, S.R., Bang, O.Y. et al. Differentially expressed genes in human peripheral blood as potential markers for statin response. J Mol Med 90, 201–211 (2012). https://doi.org/10.1007/s00109-011-0818-3

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