ZNF542P is a pseudogene associated with LDL response to simvastatin treatment
| Autor: | Yii-Der Ida Chen, Ronald M. Krauss, Marisa W. Medina, Elizabeth Theusch, Yu-Lin Kuang, Celia Cubitt, Katrina Mitchel, Andréa C. Dosé, Kyungpil Kim |
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| Rok vydání: | 2018 |
| Předmět: |
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 |
| Zdroj: | Scientific reports, vol 8, iss 1 Scientific Reports Scientific Reports, Vol 8, Iss 1, Pp 1-8 (2018) |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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