title: Association of drug transporter gene ABCB1 (MDR1) 3435C to T polymorphism with colchicine response in familial Mediterranean fever.
abstract: OBJECTIVE
  Colchicine is a mainstay of treatment in familial Mediterranean fever (FMF); however, 5%-10% of patients do not respond to colchicine. Adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1 or MDR1) is a drug transporter that extrudes colchicine out of cells. ABCB1 gene 3435C to T polymorphism has been demonstrated to alter MDR1 expression in mononuclear cells. Thus, the amount of MDR1 in mononuclear cells may alter response to colchicine. We investigated the association between MDR1 3435C to T polymorphism and colchicine response in patients with FMF.
  
  
  METHODS
  Patients (n = 120) were examined for colchicine responses. ABCB1 gene 3435C to T genotypes were determined to analyze associations with colchicine resistance.
  
  
  RESULTS
  Ninety-eight patients were evaluated as responders and 22 as nonresponders. The distributions of ABCB1 CC, CT, and TT genotypes were significantly different between responsive and nonresponsive groups (chi-square = 6.86, p = 0.032). Colchicine resistance was significantly higher in patients harboring the C allele than in patients with TT genotype (odds ratio 9.71, 95% CI 1.58-58.76). Similarly, the mean colchicine dose to prevent remission was significantly lower in the TT group compared with subjects with the C allele (p = 0.014).
  
  
  CONCLUSIONS
  Our study revealed an association between 3435C to T polymorphism and colchicine response in patients with FMF. Patients with the TT genotype for the ABCB1 3435C to T variant responded better to colchicine in terms of treatment efficacy and colchicine dose requirements.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Hacettepe University Faculty of Medicine, Sihhiye, Ankara, Turkey. tufan@hacettepe.edu.tr
authors.forename: Abdurrahman
authors.initials: A
authors.lastname: Tufan
authors.forename: Melih O
authors.initials: MO
authors.lastname: Babaoglu
authors.forename: Ali
authors.initials: A
authors.lastname: Akdogan
authors.forename: Umit
authors.initials: U
authors.lastname: Yasar
authors.forename: Meral
authors.initials: M
authors.lastname: Calguneri
authors.forename: Umut
authors.initials: U
authors.lastname: Kalyoncu
authors.forename: Omer
authors.initials: O
authors.lastname: Karadag
authors.forename: Mutlu
authors.initials: M
authors.lastname: Hayran
authors.forename: A Ihsan
authors.initials: AI
authors.lastname: Ertenli
authors.forename: Atila
authors.initials: A
authors.lastname: Bozkurt
authors.forename: Sedat
authors.initials: S
authors.lastname: Kiraz
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D003078:Colchicine / Q000627:therapeutic use*; D010505:Familial Mediterranean Fever / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006074:Gout Suppressants / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D027361:Organic Anion Transporters / Q000097:blood / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D006074:Gout Suppressants; D027361:Organic Anion Transporters; D003078:Colchicine