Influence of Cytochrome P450 (CYP) 3A4*1G on Lipid-Lowering Efficacy of Atorvastatin among Critically Ill Cardiac Egyptian Patients
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- Category: Vol. 84, September 2016
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Influence of Cytochrome P450 (CYP) 3A4*1G on Lipid-Lowering Efficacy of Atorvastatin among Critically Ill Cardiac Egyptian Patients, ENAS E.T. DWEDAR, SANAA S. ABD EL-SHAFY, SHERIF MOKHTAR and AHMED ABD EL-BARY
Abstract
Background: Atorvastatin (HMG-CoA reductase inhibitor) is mainly metabolized by cytochrome P450 (CYP) 3A4 en-zyme, 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 homozy-gotes (*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.