CYP3A5*3A allele is associated with reduced lowering-lipid response to atorvastatin in individuals with hypercholesterolemia

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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, Andre A. ; Hirata, Rosario D. C.

• Tipo de documento: Artigo Científico
• Fonte: Clinica Chimica Acta; v. 398, n. 1-2, p. 6-pg., 2008-12-01.

Resumo

Background: 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. Methods: 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. Results: >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<0.01). Non-Africans carrying *3A allele (*3C and *1D combined alleles) had lower total and LDL-cholesterol response to atorvastatin than non-*3A allele carriers (p<0.05). Conclusion: CYP3A5*3A allele is associated with reduced cholesterol-lowering response to atorvastatin in non-African individuals. (C) 2008 Elsevier B.V. All rights reserved. (AU)

• Processo FAPESP: 03/02086-8 - Estudo de polimorfismos genéticos da família ABC: efeitos na expressão gênica e na resposta farmacológica à atorvastatina
• Beneficiário: Rosario Dominguez Crespo Hirata
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 00/12224-0 - Análise das alterações no gene da enzima CYP3A4 do citocromo P450 que influenciam a resposta terapêutica às estatinas em indivíduos hipercolesterolêmicos
• Beneficiário: Rosario Dominguez Crespo Hirata
• Modalidade de apoio: Auxílio à Pesquisa - Regular