Abstract
IMPACT OF CYP3A4*1B ON THE LIPID PROFILE IN INDIVIDUALS WHO USE HMG-COA REDUCTASE INHIBITORS

Israel Higino de Sousa, Ilka Kassandra Pereira Belfort, Marcelo dos Santos, Sally Cristina Moutinho Monteiro*

ABSTRACT

Statins are part of a broadly effective group of drugs used in the treatment of dyslipidemia. Its mechanism of action is based on inhibition of the 3-hydroxy-3-methyl-glutaryl-CoA reductase enzyme (HMG-CoA reductase), resulting in a decrease in the hepatic synthesis of cholesterol and an increase in LDL receptor expression in hepatocytes. Objective: This study aimed to investigate the effect of the polymorphic gene CYP3A4 (−392A>G) on the lipid profile in hypercholesterolemic individuals treated with statins in São Luis (Maranhão State, Brazil). Methods: A total of 201 volunteers diagnosed with hypercholesterolemia who were using statin (10 mg/day) were investigated. Total cholesterol, HDL cholesterol, and triglyceride (after 12 hours fasting) concentrations were determined by enzymatic methods. LDL cholesterol was calculated by the Friedewald formula when the triglyceride concentration did not exceed 400 mg/dL. PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) was used to detect CYP3A4 –392A>G polymorphism. Results: The distribution of genotypes for the variant CYP3A4 (−392A>G) allele was: AA = 75.1%, AG = 21.9%, and GG = 3.0%. Allele and genotype frequencies were in Hardy-Weinberg equilibrium (p = 0.502). The serum levels of total cholesterol (AA = 164.0 ± 37.9 vs. GG = 233.1 ± 66.8, p<0.005) and LDL cholesterol (AA = 92.8 ± 32.4 vs. GG = 150.0 ± 59.4, p<0.05) showed different concentrations among individuals with allele AA vs. GG. Conclusion: This study suggests that the total cholesterol and LDL cholesterol levels are influenced by the variant CYP3A4 (−392A>G) allele in individuals who use statins.

Keywords: polymorphism, CYP3A4, statin.


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