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ZNF542P is a pseudogene associated with LDL response to simvastatin treatment
- Source :
- Scientific reports, vol 8, iss 1, Scientific Reports, Scientific Reports, Vol 8, Iss 1, Pp 1-8 (2018)
- Publication Year :
- 2018
- Publisher :
- eScholarship, University of California, 2018.
-
Abstract
- Statins are the most commonly prescribed cardiovascular disease drug, but their inter-individual efficacy varies considerably. Genetic factors uncovered to date have only explained a small proportion of variation in low-density lipoprotein cholesterol (LDLC) lowering. To identify novel markers and determinants of statin response, we used whole transcriptome sequence data collected from simvastatin and control incubated lymphoblastoid cell lines (LCLs) established from participants of the Cholesterol and Pharmacogenetics (CAP) simvastatin clinical trial. We looked for genes whose statin-induced expression changes were most different between LCLs derived from individuals with high versus low plasma LDLC statin response during the CAP trial. We created a classification model of 82 “signature” gene expression changes that distinguished high versus low LDLC statin response. One of the most differentially changing genes was zinc finger protein 542 pseudogene (ZNF542P), the signature gene with changes most correlated with statin-induced change in cellular cholesterol ester, an in vitro marker of statin response. ZNF542P knock-down in a human hepatoma cell line increased intracellular cholesterol ester levels upon simvastatin treatment. Together, these findings imply a role for ZNF542P in LDLC response to simvastatin and, importantly, highlight the potential significance of noncoding RNAs as a contributing factor to variation in drug response.
- Subjects :
- 0301 basic medicine
Simvastatin
Statin
medicine.drug_class
Pseudogene
lcsh:Medicine
Pharmacology
Cardiovascular
Article
Cell Line
LDL
Transcriptome
03 medical and health sciences
chemistry.chemical_compound
Clinical Research
Cell Line, Tumor
Gene expression
medicine
Genetics
2.1 Biological and endogenous factors
Humans
cardiovascular diseases
Aetiology
lcsh:Science
Gene
Multidisciplinary
Tumor
Cholesterol
business.industry
lcsh:R
Human Genome
nutritional and metabolic diseases
Cholesterol, LDL
Atherosclerosis
3. Good health
030104 developmental biology
Good Health and Well Being
chemistry
Pharmacogenetics
lcsh:Q
lipids (amino acids, peptides, and proteins)
business
Pseudogenes
medicine.drug
Biotechnology
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Scientific reports, vol 8, iss 1, Scientific Reports, Scientific Reports, Vol 8, Iss 1, Pp 1-8 (2018)
- Accession number :
- edsair.doi.dedup.....723cf6ba4000ae8cb7417543f14a28fa