No effect of CYP3A4 intron 6 C>T polymorphism (CYP3A4*22) on lipid-lowering response to statins in Greek patients with primary hypercholesterolemia

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