Abstract

The Relationship of Disease Activity and Colchicine Resistance in Patients with Familial Mediterranean Fever with CYP3A4, CYP2D6, and MDR1 Gene Variants

Author(s): Busra Bilim Turkcan, Aslı Toylu, Elif Comak , Mustafa Koyun, Sema Akman

The Relationship of Disease Activity and Colchicine Resistance in Patients with Familial Mediterranean Fever with CYP3A4, CYP2D6, and MDR1 Gene Variants ABSTRACT Background: Colchicine is the mainstay of Familial Mediterranean Fever (FMF) treatment. The molecules responsible for colchicine metabolism are CYP3A4, CYP2D6, and MDR1. We aimed to determine the frequency of MDR1 c.3435C>T, CYP3A41b c.-392G>A, CYP2D6*4 c.1934G>A, and CYP2D6*3c.2637Adel variants in healthy and patient groups, and to examine the relation between these variants and colchicine resistance. Methods: This cross-sectional study was performed between January 2019 and Fabruary 2019. The patient group consisted of children aged 3-18 years having a mutation in the MEFV gene who were diagnosed according to Turkish Pediatric FMF criteria. Children without any underlying chronic disease were considered as the control group. Data were obtained from face-to-face appointments and medical records. Results: Overall, 124 children with FMF and 60 healthy children were enrolled. The variant distributions were similar in both groups. There was no statistically significant difference between the variant distribution and colchicine resistance (p>0.05). However, the dose of colchicine used was significantly lower in those with the MDR1 mutant allele and those with CYP2D6*4 mutation compared to other patients (p<0.05). Conclusion: Although several allele variants responsible for colchicine metabolism are unrelated to colchicine resistance, MDR1 and CYP2D6*4 mutations can predict a lower dose of colchicine need.