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Journal of Molecular Medicine

, Volume 90, Issue 2, pp 201–211 | Cite as

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

  • Hong-Hee Won
  • Suk Ran Kim
  • Oh Young Bang
  • Sang-Chol Lee
  • Wooseong Huh
  • Jae-Wook Ko
  • Hyung-Gun Kim
  • Howard L. McLeod
  • Thomas M. O’Connell
  • Jong-Won Kim
  • Soo-Youn LeeEmail author
Original Article

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.

Keywords

Cholesterol Statin Pharmacogenomics Gene array analysis Gene expression 

Notes

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).

Conflicts of interest

None.

Supplementary material

109_2011_818_MOESM1_ESM.xls (40 kb)
Supplementary Table 1 Differentially expressed genes between the high LDL group (n = 10) and the low LDL group (n = 10; XLS 39 kb)
109_2011_818_MOESM2_ESM.xls (20 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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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Hong-Hee Won
    • 1
    • 2
  • Suk Ran Kim
    • 3
  • Oh Young Bang
    • 4
  • Sang-Chol Lee
    • 5
  • Wooseong Huh
    • 5
    • 6
  • Jae-Wook Ko
    • 6
  • Hyung-Gun Kim
    • 7
  • Howard L. McLeod
    • 8
  • Thomas M. O’Connell
    • 9
  • Jong-Won Kim
    • 3
  • Soo-Youn Lee
    • 3
    • 6
    Email author
  1. 1.Samsung Biomedical Research InstituteSamsung Medical CenterSeoulSouth Korea
  2. 2.Department of Bio and Brain EngineeringKorea Advanced Institute of Science and TechnologyDaejeonSouth Korea
  3. 3.Department of Laboratory Medicine and Genetics, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulSouth Korea
  4. 4.Department of Neurology, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulSouth Korea
  5. 5.Department of Medicine, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulSouth Korea
  6. 6.Department of Clinical Pharmacology and TherapeuticsSamsung Medical CenterSeoulSouth Korea
  7. 7.Department of Pharmacology, College of MedicineDankook UniversityChonanSouth Korea
  8. 8.UNC Institute for Pharmacogenomics and Individualized TherapyUniversity of North CarolinaChapel HillUSA
  9. 9.Division of Pharmacotherapy and Experimental Therapeutics, School of PharmacyUniversity of North Carolina at Chapel HillChapel HillUSA

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