The contribution of genotypes at the MEFV and SAA1 loci to amyloidosis and disease severity in patients with familial mediterranean fever

Ruth Gershoni-Baruch, Riva Brik, Nurit Zacks, Maruan Shinawi, Merav Lidar, Avi Livneh

Research output: Contribution to journalArticle

145 Scopus citations

Abstract

Objective. The clinical profile in familial Mediterranean fever (FMF), including its major manifestation, amyloidosis, is influenced by MEFV allelic heterogeneity and other genetic and/or environmental factors. In this study, we analyzed the contribution of genotypes at the MEFV and SAA1 loci to disease severity and to the development of amyloidosis, and further defined the factors affecting the clinical profile of FMF. Methods. We investigated a sample of 277 FMF patients (154 men and 123 women), including 62 patients with nephropathic amyloidosis, in whom both FMF alleles had been identified. A detailed chart review, interview, and physical examination were undertaken to determine the patients' demographic characteristics, medical history, clinical manifestations, and treatment. The disease severity score was calculated from the Tel-Hashomer key. Genotypes at the SAA1 locus (isoforms α, β, and γ) were determined in all patients. The SAA1 13C/T polymorphism of the SAA1 promotor was analyzed in a subset of cases. Results. The male:female ratio (154:123, or 1.3) was higher among patients with amyloidosis (40:22, or 1.8) compared with patients without amyloidosis (114:101, or 1.1). Logistic regression analysis showed that homozygosity for the M694V allele (odds ratio [OR] 4.27, 95% confidence interval [95% CI] 2.01-9.07), the presence of the SAAa/a genotype (OR 2.99, 95% CI 1.47-6.09), the occurrence of arthritis attacks (OR 2.43, 95% CI 1.17-5.06), and male sex (OR 1.73, 95% CI 0.90-3.33) were significantly and independently associated with renal amyloidosis. Disease severity was mainly influenced by MEFV mutations and was not associated with genotypes at the SAA1 locus. The SAA1 13T allele was rare, being associated mainly with the SAA γ isoform, and not related to renal amyloidosis. Conclusion. Overall, disease severity and the development of amyloidosis in FMF are differentially affected by genetic variations within and outside the MEFV gene.

Original languageEnglish
Pages (from-to)1149-1155
Number of pages7
JournalArthritis and rheumatism
Volume48
Issue number4
DOIs
StatePublished - Apr 1 2003
Externally publishedYes

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