Country as the primary risk factor for renal amyloidosis in familial Mediterranean fever

Area of Science:

• Genetics and Molecular Biology
• Rheumatology and Immunology
• Nephrology

Background:

• Familial Mediterranean fever (FMF) is a prototypic autoinflammatory disorder caused by MEFV gene mutations.
• Renal amyloidosis is a severe complication of FMF, historically linked to the M694V mutation.
• Previous studies on M694V and amyloidosis risk have yielded conflicting results due to study design and limited covariable analysis.

Purpose of the Study:

• To investigate the relative contributions of MEFV genotype and epidemiologic factors to renal amyloidosis risk in FMF patients.
• To clarify the controversial association between specific MEFV mutations and amyloidosis susceptibility.
• To identify key determinants of renal amyloidosis in a large, genetically confirmed FMF cohort.

Main Methods:

• A global online survey was conducted via the MetaFMF database, collecting data from 35 centers across 14 countries.
• Data from 2,482 genetically confirmed FMF patients, including 260 with renal amyloidosis, were analyzed.
• Standardized data collection ensured the retrieval of crude initial data for analysis.

Main Results:

• Amyloid nephropathy was diagnosed in 11.4% of the studied FMF patients.
• Country of recruitment emerged as the primary risk factor for renal amyloidosis (OR 3.2), surpassing M694V homozygosity, proband status, and disease duration.
• Stratified analyses by country revealed differing risk factor profiles.

Conclusions:

• Geographic origin, not solely MEFV genotype, is the principal determinant of renal amyloidosis risk in FMF.
• The observed geographical variation in risk, correlating with infant mortality rates, suggests potential environmental influences on amyloidosis susceptibility.
• Colchicine prophylaxis should be considered based on country of origin alongside MEFV genotype, particularly for M694V homozygotes.