Genotype-phenotype correlation in patients with familial Mediterranean fever in East Anatolia (Turkey).

AIMS: Familial Mediterranean fever (FMF) is an autosomal recessive hereditary disease. Clinical symptoms and findings (phenotypes) seen in this disease are generally fever, abdominal pain, and arthritis. Amyloidosis is also a significant complication. Phenotype-genotype correlations in FMF have not been conclusively resolved. The aims of this study were to find the most frequent mutation/genotype of FMF, as well as to investigate the role of genetic factors on the phenotype and on the development of amyloidosis in a population living in East Anatolia (Turkey). This study included 105 adult patients with FMF. DNA samples were obtained from peripheral blood lymphocytes of the patients. Mutations of the Mediterranean fever (MEFV) gene were analyzed with an FMF Strip Assay test kit (ViennaLab Labordiagnostika GmbH, Vienna, Austria). Patients were separated according to genotypes, and phenotypes were compared statistically by the chi-square test.

RESULTS: The most frequent mutation was M694V (53%) and the most frequent genotype was M694V/M694V (26%). In total, 81% of the patients experienced abdominal pain, 76% had fever, and 22% had arthritis. Fever and arthritis were determined in similar ratios to other genotypes (76% and 19%, respectively) in the M694V/M694V genotype (74% and 29%, respectively) (p > 0.50 and p > 0.20, respectively). However, the patients without the M694V/M694V genotype (86%) had a higher abdominal pain ratio than did the patients with the M694V/M694V genotype (67%) (p <0.05). Renal amyloidosis was determined in 33% of both M694V/M694V and M680I(G/C)/M680I(G/C) homozygous groups and in 12% of the heterozygous groups (p < 0.02 and p < 0.00002, respectively). In other words, homozygous groups had higher ratios of renal amyloidosis.

CONCLUSIONS: The most frequent mutation in FMF was M694V and the most frequent genotype was M694V/M694V. Fever, abdominal pain, arthritis, and renal amyloidosis were determined not only in patients with M694V/M694V genotype but also in other genotypes. Therefore, genotypes may not predict phenotypes in FMF. Renal amyloidosis was seen more frequently in homozygous genotypes.