Unresponsiveness to colchicine therapy in patients with familial Mediterranean fever homozygous for the M694V mutation.
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.
Soylemezoglu
Oguz
O
Department of Pediatric Nephrology, Gazi University Medical Hospital, Ankara, Turkey.
Arga
Mustafa
M
Fidan
Kibriya
K
Gonen
Sevim
S
Emeksiz
Hamdi Cihan
HC
Hasanoglu
Enver
E
Buyan
Necla
N
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
D003078:Colchicine