The role of effıcacy of CYP3A4 and MDR1 gene polymorphısms on colchıcıne pharmacogenetıcs ın the treatment of famılıal medıterranean fever

The most efficient therapeutic agent in treatment of ?Familiar Mediterranean Fever?(AAA) is colchicine. Colchicine is a two-way treatment applied in preventing the development of seconder amyloidosis and decreasing the intensity of attack frequency of disease. However, 5-10% of patients respond to the treatment show resistance. The differences of the response to the treatment in each person result from the changes in control mechanisms controlling pharmacokinetic and pharmacodynamic of drug. The differences in colchicine pharmacokinetic are related to CYP3A4 which is member of Cytochrome P450 enzyme family and MDR1/P-gp which is member of ABCB1 transmembran protein family.We searched the relationship among MEFV gene mutations of 78 patients having treatment of colchicine in different dosages during over one year, clinical findings of disease, CYP3A4 and MDR1/P-gp polymorphisms. 3435C>T polymorphism from ABCB1 gene polymorphisms was evaluated with the method of ?Restriction Fragment Lenght Polymorphism? (RFLP) in whole patients. 1B(-392A>G), *2(15713T>C), *3(23171T>C), *12(21896C>T) and *17(15615T>C) from CYP3A4 gene polymorphisms in 46 patients and (-)1A>G, 61A>G, 1199G>A, 1236C>T, 2677G>A, 2677G>T polymorphisms from MDR1/P-gp gene polymorphisms in 48 patients were evaluated by using full automated microarray analyzer (INFINITITM Autogenomics, Inc., Vista, CA) with the capture probes were fluorescently labeled using analyte specific primer extension, hybridized to a microarray and then scanned.Consequently, there weren?t a statistically significant correlation (p=0,13) between 3435C>T genotype alternatives and MEFV gene mutations with colchicine treatment dosage on patients of our group. There were a statistically significant correlation among patients treated with 3x1/day and 2x1/day colchicine dosages and 2677G>T polymorphism (p=0.032). Among the symptoms of the disease, there were a statistically significant correlation with arthritis and 3435C>T polymorphism (p=0.04), peritonitis and 1199G> A polymorphism (p=0.01), pleuritis with 2677G>A (p=0.02), 15713T>C (p=0.02) and 15615T>C (p=0.02) polymorphisms.