Amyloidosis in familial Mediterranean fever patients: correlation with MEFV genotype and SAA1 and MICA polymorphisms effects

Myrna Medlej-Hashim¹ , Valérie Delague¹ , Eliane Chouery¹ , Nabiha Salem¹ , Mohammed Rawashdeh² , Gérard Lefranc³ , Jacques Loiselet¹ and André Mégarbané¹

¹Unité de Génétique Médicale. Faculté de Médecine, Université Saint Joseph, Beirut, Lebanon

²Division of Gastroenterology. Department of Pediatrics, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan

³Laboratoire d'Immunogénétique Moléculaire, Institut de Génétique Humaine, CNRS UPR 1142 et Université Montpellier II, France

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BMC Medical Genetics 2004, 5:4doi:10.1186/1471-2350-5-4


Published:	10 February 2004

Abstract

Background

Familial mediterranean fever (FMF) is a recessively inherited disease characterized by recurrent crises of fever, abdominal, articular and/or thoracic pain. The most severe complication is the development of renal amyloidosis. Over 35 mutations have been discovered so far in the gene responsible for the disease, MEFV. This article aims at determining a correlation between the MEFV genotype and the occurence of amyloidosis in FMF patients, in addition to the study of the modifying effects of the SAA1 (type 1 serum amyloid A protein) and MICA (Major Histocompatibility Complex (MHC) class-I-chain-related gene A) genes on this severe complication.

Methods

Fourteen MEFV mutations were screened and the SAA1 and MICA polymorphisms tested in 30 FMF patients with amyloidosis and 40 FMF patients without amyloidosis.

Results

The M694V and V726A allelic frequencies were, respectively, significantly higher and lower in the group with amyloidosis, compared to the control FMF group. The beta and gamma SAA1 alleles were more frequently encountered in the group without amyloidosis, whereas the alpha allele was significantly more observed in FMF patients with amyloidosis (p < 0.025). All the MICA alleles were encountered in both patients' groups, but none of them was significantly associated with amyloidosis.

Conclusions

The results suggest a protective effect of the SAA1 beta and gamma alleles on the development of amyloidosis and show the absence of a MICA modifying effect on amyloidosis development. Testing these polymorphisms on a larger sample will lead to more definite conclusions.