Association between colchicine responsiveness and CYP3A4 polymorphisms (CYP3A4*1B, *2, *17) in patients with familial Mediterranean fever on colchicine therapy

Familial Mediterranean fever (FMF) is an autoinflammatory disease characterized by recurrent attacks of fever, peritonitis, arthritis, pleuritis and eryzpel-like erythema. Colchicine prevents attacks in most of the patients. However, 5-15 % of the patients suffer from attacks despite taking colchicine regularly, and factors involved in colchicine unresponsiveness in these patients has not been clarified up to now. Colchicine is metabolised by cytochrome P450 3A4 (CYP3A4), and polymorphisms in the promoter and coding regions of this enzyme may alter the expression and activity of CYP3A4 and cause differences in colchicine response in patients with FMF. We investigated in this study whether an association exists between CYP3A4*1B, *2, *17 polymorphisms and colchicine response in patients with FMF. The study group included 203 patients (69 male, 134 female), and the healthy control (HC) group included 50 individuals (17 male, 33 female). Patients who had more than one attack in 3 months while adhering to a colchicine regimen of ?2 mg/day were defined as unresponsive to colchicine. Blood samples were drawn by venipuncture, collected in an EDTA tube and stored at -200C until analyzed. Analysis of CYP3A4 polymorphisms was done using real-time polymerase chain reaction (real-time PCR). Twenty six patients were unresponsive to colchicine therapy. There were no CYP3A4*1B or *17 polymorphisms either in the patients or HCs. Nine patients were heterozygote for CYP3A4*2 polymorphism (TC genotype, 4.4 %), and frequency of allele C was 2.2 %. CYP3A4*2 was not detected in HCs. There was no statistically significant difference with respect to the frequency of CYP3A4 polymorphisms between colchicine nonresponsive and responsive patients, as well as between patients and HCs. We did not find an association between CYP3A4*1B, *2 and *17 polymorphisms and colchicine responsiveness. Factors other than these polymorphisms may be involved in nonresponsiveness to colchicine therapy.