Influence of Cytochrome P450 (CYP) 3A4*1G on Lipid-Lowering Efficacy of Atorvastatin among Critically Ill Cardiac Egyptian Patients

Background: Atorvastatin (HMG-CoA reductase inhibitor) is mainly metabolized by cytochrome P450 (CYP) 3A4 enzyme, genetic variation within the CYP3A4 gene may lead to variation in CYP3A4 activity and, in turn, to the difference in the metabolism and, ultimately, the variable response of atorvastatin. Methodology: We conduct this study on 48 critically cardiac patients with myocardial infarction who prospectively received atorvastatin (80mg/day p.o./4 weeks) from July 2011 to May 2015. Genotyping of CYP3A4* 1 G was performed by a Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) analysis. Total Cholesterol (TC), serum Triglyceride (TG), Low-density Lipoprotein Cholesterol (LDL-C), and High-Density Lipoprotein Cholesterol (HDL-C) levels were determined before and after treatment by enzymatic assays. Results: The frequency of CYP3A4*1G in Egyptian hyperlipidemic cardiac patients was 0.34. Among the 48 subjects, there were 20 wildtype homozygotes (*1/*1), 23 heterozygotes (*1/*1G), and 5 mutant homozygotes (*1G/*1G) for CYP3A4*1G. After treatment with 80mg atorvastatin daily for 4 weeks, TC, TG, and LDL-C and HDL-C concentrations were de-creased from baseline, on average, by 26.51±7.38%, 17.64± 10.44%, 32.69±10.02%, and –6.68±3.49%, respectively (p 0.001). After atorvastatin treatment, the mean percentage reduction in serum TC was 23.71±5.68% (*1/*1), 26.31±6.61% (*1/*1G), and 38.59±4.95% (*1G/*1G), respectively, the mean percentage reduction in serum TG was 15.02±8.1% (*1/*1), 16.96±10.25% (*1/*1G), and 31.27±11.09% (*1G/ * 1 G) and the mean percentage reduction in serum LDL-C was 29.73±9.14% (*1/*1), 32.06±8.6% (*1/*1G), and 47.42±7.75% (*1G/*1G) Conclusion: Carrying CYP3A4*1G increase the lipid-lowering efficacy of atorvastatin among Egyptian populations.