No effect of CYP3A4 intron 6 C>T polymorphism (CYP3A4*22) on lipid-lowering response to statins in Greek patients with primary hypercholesterolemia
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Georgia Ragia
Abstract
Background: Interindividual variability exists in statin lipid-lowering response, partially attributed to genetic factors. CYP3A4 intron 6 C>T polymorphism (CYP3A4*22 allele, rs35599367) has been recently identified and was associated with reduced CYP3A4 expression. We analyzed the association of CYP3A4*22 allele with response to atorvastatin and simvastatin.
Methods: A total of 416 statin-treated (207 atorvastatin- and 209 simvastatin-treated) adults with primary hypercholesterolemia were included in the study. Total cholesterol and low-density lipoprotein cholesterol were measured at baseline and on 6 months of treatment. CYP3A4*22 allele was analyzed with TaqMan assay.
Results: In the entire cohort population, 41 individuals carried CYP3A4*22 allele (18 in atorvastatin and 23 in simvastatin treatment). CYP3A4*22 allele was not associated with lipid-lowering response to atorvastatin or simvastatin. No sex-gene or statin dose-gene interaction was observed in either statin-treated patient cohort.
Conclusions: The effect of CYP3A4*22 allele on lipid-lowering response to CYP3A metabolized statins, if present, can potentially be masked by relevant confounding or uncontrolled factors; therefore, further population-driven studies are required.
Acknowledgments
Laure Elens is a postdoctoral researcher with the Fonds National de la Recherche Scientifique (FRS-FNRS), Belgium.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: Funding for this study was from the Department’s regular budget. No sponsors were involved.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
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Articles in the same Issue
- Frontmatter
- Editorial
- From DMDI “Drug Metabolism and Drug Interactions” to DMPT “Drug Metabolism and Personalized Therapy”
- Review
- Clinical drug-drug interactions: focus on venlafaxine
- Reviews in Population Pharmacogenomics
- Pharmacogenetics in Central American healthy volunteers: interethnic variability
- Genomic biomarkers related to drug response in Venezuelan populations
- Originial Articles
- No effect of CYP3A4 intron 6 C>T polymorphism (CYP3A4*22) on lipid-lowering response to statins in Greek patients with primary hypercholesterolemia
- Chloral hydrate, through biotransformation to dichloroacetate, inhibits maleylacetoacetate isomerase and tyrosine catabolism in humans
- Effect of rifampin on the pharmacokinetics of bosutinib, a dual Src/Abl tyrosine kinase inhibitor, when administered concomitantly to healthy subjects
- Minor contribution of biliary excretion in lithium elimination in rats
- Case Report
- Fatal hyperkalemia following succinylcholine administration in a child on oral propranolol
