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

Genet Mol Res. 2013 Jan 24;12(3):3521-8. doi: 10.4238/2013.January.24.2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
  • Adolescent
  • Adult
  • Colchicine / administration & dosage*
  • Cytochrome P-450 CYP3A / genetics*
  • Familial Mediterranean Fever / drug therapy
  • Familial Mediterranean Fever / genetics*
  • Familial Mediterranean Fever / pathology
  • Haplotypes
  • Humans
  • Male
  • Middle Aged
  • Pharmacogenetics
  • Polymorphism, Single Nucleotide
  • Turkey
  • Young Adult

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human
  • Colchicine