CYP3A53A allele is associated with reduced lowering-lipid response to atorvastatin in individuals with hypercholesterolemia

• Published in: Clinica chimica acta 2008-12, Vol.398 (1-2), p.15-20
• Main Authors: Willrich, Maria Alice V, Hirata, Mario H, Genvigir, Fabiana D V, Arazi, Simone S, Rebecchi, Ivanise M M, Rodrigues, Alice C, Bernik, Marcia M S, Dorea, Egidio L, Bertolami, Marcelo C, Faludi, André A, Hirata, Rosario D C
• Format: Article
• Language: English
• Subjects: African Continental Ancestry Group; Aged; Alleles; Atorvastatin Calcium; Body Mass Index; Brazil - epidemiology; Cholesterol, LDL - blood; Cytochrome P-450 CYP3A - genetics; DNA - genetics; DNA Primers; Female; Gene Frequency; Genotype; Heptanoic Acids - therapeutic use; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Hypercholesterolemia - drug therapy; Hypercholesterolemia - epidemiology; Hypercholesterolemia - genetics; Male; Middle Aged; Polymorphism, Restriction Fragment Length; Pyrroles - therapeutic use; Reverse Transcriptase Polymerase Chain Reaction
• ISSN: 0009-8981
• DOI: 10.1016/j.cca.2008.07.032

The cytochrome P450 isoenzyme 3A5 (CYP3A5) has an important role on biotransformation of xenobiotics. CYP3A5 SNPs have been associated with variations on enzyme activity that can modify the metabolism of several drugs. In order to evaluate the influence of CYP3A5 variants on response to lowering-cholesterol drugs, 139 individuals with hypercholesterolemia were selected. After a wash-out period of 4 weeks, individuals were treated with atorvastatin (10 mg/day/4 weeks). Genomic DNA was extracted by a salting-out procedure. CYP3A5*3C, CYP3A5*6 and CYP3A5*1D were analyzed by PCR-RFLP and DNA sequencing. >Frequencies of the CYP3A5*3C and CYP3A5*1D alleles were lower in individuals of African descent (*3C: 47.8% and *1D: 55.2%) than in non-Africans (*3C: 84.9% and *1D 84.8%, p