title: Unresponsiveness to colchicine therapy in patients with familial Mediterranean fever homozygous for the M694V mutation.
abstract: OBJECTIVE
  More than 50 disease-associated mutations of the Mediterranean fever gene (MEFV) have been identified in familial Mediterranean fever (FMF), some of which were shown to have different clinical, diagnostic, prognostic, and therapeutic implications. The aim of our study was to define the frequency of mutation type, genotype-phenotype correlation, and response to colchicine treatment in patients with FMF.
  
  
  METHODS
  This study included 222 pediatric FMF patients. All patients were investigated for 6 MEFV mutations. Then patients were divided into 3 groups according to the presence of M694V mutation on both of the alleles (homozygotes), on only 1 allele (heterozygotes), and on none of the alleles, and compared according to their phenotypic characteristics and response to treatment. M694V/M694V was denoted Group A, M694V/Other Group B, and Other/Other, Group C.
  
  
  RESULTS
  Complete colchicine response was significantly lower while the rate of unresponsiveness was significantly higher in Group A compared to Groups B and C (p = 0.031, p < 0.001 and p = 0.005, p = 0.029, respectively). No differences except proteinuria were found between the phenotypic features of 3 groups. Group C had the lowest rate of proteinuria development (p = 0.024). All the amyloidosis patients were in Group A.
  
  
  CONCLUSIONS
  Our results indicate that the M694V/M694V mutation is associated with lower response to colchicine treatment. Therefore, patients homozygous for M694V/M694V may be carrying an increased risk for development of amyloidosis.
authors.affiliation: Department of Pediatric Nephrology, Gazi University Medical Hospital, Ankara, Turkey.
authors.forename: Oguz
authors.initials: O
authors.lastname: Soylemezoglu
authors.forename: Mustafa
authors.initials: M
authors.lastname: Arga
authors.forename: Kibriya
authors.initials: K
authors.lastname: Fidan
authors.forename: Sevim
authors.initials: S
authors.lastname: Gonen
authors.forename: Hamdi Cihan
authors.initials: HC
authors.lastname: Emeksiz
authors.forename: Enver
authors.initials: E
authors.lastname: Hasanoglu
authors.forename: Necla
authors.initials: N
authors.lastname: Buyan
mesh_terms: D002648:Child; D002675:Child, Preschool; D003078:Colchicine / Q000627:therapeutic use*; D010505:Familial Mediterranean Fever / Q000188:drug therapy / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype
chemical_list: D003078:Colchicine