Lack of an effect of CYP3A4 and MDR1 gene polymorphisms on colchicine pharmacogenetics in the treatment of Familial Mediterranean fever


Dogruer D., Tuğ E., Bes C., Soy M.

GENETICS AND MOLECULAR RESEARCH, vol.12, no.3, pp.3521-3528, 2013 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 12 Issue: 3
  • Publication Date: 2013
  • Doi Number: 10.4238/2013.january.24.2
  • Journal Name: GENETICS AND MOLECULAR RESEARCH
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.3521-3528
  • Gazi University Affiliated: Yes

Abstract

The P-gp/MDR1 multidrug transporter mediates detoxification of numerous drugs, including colchicine, and CYP3A4 is key to the biotransformation of colchicine. We investigated the effects of CYP3A4 and P-gp/MDR1 polymorphisms on bioavailability of colchicine in patients with Familial Mediterranean fever (FMF). Forty-eight Turkish patients with FMF treated with colchicine were genotyped for 3435C>T, (-)1A>G, 61A>G, 1199G>A, 1236C>T, 2677G>A, 2677G>T polymorphisms in the P-gp/MDR1 gene and 3435C>T, *1B(-392A>G), *2(15713T>C), *3(23171T>C), *12(21896C>T), *17(15615T>C) polymorphisms in the CYP3A4 gene. Doses of colchicine administered to patients did not differ with respect to P-gp/MDR1 or CYP3A4 gene polymorphism. We also determined the genotype distributions of CYP3A4 and P-gp/MDR1 genes among FMF patients. There was no significant gender difference in the P-gp/MDR1 polymorphism, whereas there were significant gender differences in the frequencies of 15713T>C and 15615T>C polymorphisms in the CYP3A4 gene. No significant relationship was found between colchicine doses that would introduce optimal clinical response and affect the therapeutic dose and CYP3A4 and P-gp/MDR1 gene polymorphisms in these FMF patients.