Abstract: MEFV Mutations in Patients with Familial Mediterranean Fever in the Black Sea Region of Turkey

MEFV Mutations in Patients with Familial Mediterranean Fever in the Black Sea Region of Turkey

SERBULENT YIGIT, HASAN BAGCI, OZAN OZKAYA, KAZIM OZDAMAR, KUDDUSI CENGIZ, and TEKIN AKPOLAT

ABSTRACT.

Objective. To investigate MEFV mutations among patients with familial Mediterranean fever (FMF), their relatives, and healthy controls in the Black Sea region of Turkey; to compare 3 different MEFV mutation analysis methods; to evaluate the role of MEFV mutations in the diagnosis of FMF; and to investigate the role of M694V in the development of amyloidosis.

Methods. In total, 890 subjects (625 patients, 165 relatives, 100 healthy controls) were included in this prospective study. MEFV mutations were studied with the amplification refractory mutation system (ARMS; n = 335), polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP; n = 335), and reverse hybridization assay (FMF StripAssay; n = 693).

Results. All methods were used in 79 patients. The ratio of false negativity was about 2% using ARMS compared to PCR-RFLP. The FMF StripAssay was used to investigate 9 more mutations and detected 17 mutations in 14 patients. The M694V/M694V genotype was more common in patients with amyloidosis (37%) compared to patients without amyloidosis (18%) (p = 0.009). The frequency of MEFV carriers was 27%. The frequency of individuals having 2 mutations among asymptomatic relatives of FMF patients was 6%.

Conclusion. The FMF StripAssay is a reliable and time-saving method. In spite of detection of new mutations and developments in MEFV assay technology, there were patients in whom no mutation was detected. Our data, combined with previous studies, show that patients having M694V/M694V carry a risk for amyloidosis. (First Release Dec 1 2007; J Rheumatol 2008;35:106-13)

Key Indexing Terms:

FAMILIAL MEDITERRANEAN FEVER
MEFV
DIAGNOSIS
BLACK SEA REGION
AMYLOIDOSIS

From the Department of Medical Biology, Ondokuz Mayis University, Samsun, Turkey.

Supported by the Research Fund of Ondokuz Mayis University (grant no. T-284).

S. Yigit, PhD; H. Bagci, PhD, Professor, Department of Medical Biology; O. Ozkaya, MD, Associate Professor, Department of Pediatric Nephrology; K. Cengiz, MD, Professor; T. Akpolat, MD, Professor, Department of Nephrology, Ondokuz Mayis University; K. Ozdamar, PhD, Professor, Department of Biostatistics, Orhangazi University, Eskisehir, Turkey.

Address reprint requests to Dr. O. Özkaya, Department of Pediatric Nephrology, Faculty of Medicine, Ondokuz Mayis University, Kurupelit, Samsun, Turkey. E-mail: ozanozkaya@yahoo.com

Accepted for publication September 4, 2007.