MEFV Mutations and CYP3A4 Polymorphisms Do Not Predict "Colchicine Responsiveness" in Familial Mediterranean Fever

Akalin T., HAZNEDAROĞLU Ş., ERGÜN M. A. , Tezcan E., Kaya A., TUFAN A., ...More

INTERNATIONAL JOURNAL OF HUMAN GENETICS, vol.14, no.1, pp.27-32, 2014 (Peer-Reviewed Journal) identifier identifier

  • Publication Type: Article / Article
  • Volume: 14 Issue: 1
  • Publication Date: 2014
  • Doi Number: 10.1080/09723757.2014.11886224
  • Journal Indexes: Science Citation Index Expanded, Scopus
  • Page Numbers: pp.27-32


Familial Mediterranean Fever (FMF) is an auto-inflammatory disease caused by mutations in the MEFV gene. Colchicine is the mainstay of FMF treatment. It is metabolised by cytochrome P450-3A4 (CYP3A4), enzyme. About 10-15% of FMF patients do not respond to treatment with colchicine. In this study, the researchers aimed to investigate association of colchicine non-responsiveness with MEFV mutations, CYP3A4*1B, *2, and *17 polymorphisms, and some demographic features of FMF patients. One hundred and ninety-six consecutive FMF patients (170 colchicine responders and 26 non-responders) were included in the study. CYP3A4 polymorphisms were detected using polymerase chain reaction and TaqMan probes CYP3A4*1B and *17 were not detected in responders or non-responders. CYP3A4*2 was detected in eight responders, all of which were in heterozygous state. However, the difference was not statistically significant. Most patients (165 responders and 25 non-responders) had MEFV gene analysis available prior to participation in the study. Frequencies for M694V, M680I, V726A, and E148Q mutations and M694V/M694V genotype were similar in two groups. Mean body mass index of responders was not significantly different from that of non-responders. Attack frequency and proteinuria level were significantly higher in non-responders than in responders. Earlier age at disease onset was found to be associated with colchicine non-responsiveness. However, neither MEFV mutations nor CYP3A4 mutations were associated with colchicine non-responsiveness.