Association between serum amyloid A1 genotype and age of onset restricts to M694 homozygote familial Mediterranean fever patients in Armenia

Objective. Familial Mediterranean fever (FMF) is an autosomal-recessive, inflammatory disorder characterised by short, recurrent attacks of fever, accompanied by pain in the abdomen, chest, or joints and complications of amyloidosis. Recently, we observed a significant association between the serum amyloid A1 (SAA1) beta/beta genotype and a delayed disease onset in 386 M694V homozygous FMF patients. This follow-up study was conducted to additionally analyse MEFV genotypes other than M694V/M694V for a possible influence of the SAA1 genotype on the age of disease onset. Methods. A total of 700 Armenian patients diagnosed with FMF based on the Tel-Hashomer criteria and carrying two MEFV mutant alleles were included in this study. Patients were divided into three MEFV genotypic subgroups: M694V homozygotes (M694V/M694V), M694V compound heterozygotes (M694V/Other), and patients with genotypes excluding M694V (Other/Other). MEFV and SAA1 analyses were performed by a commercial reverse-hybridisation assay, and resulting genotypes were matched against the demographic and clinical characteristics of the patients. Results. Within the subgroup of M694/M694 homozygotes, SAA1 genotype beta/beta could be identified in 115 (34.43%) and 32 (61.54%) patients with an age of onset <20 and >= 20 years, respectively (p<0.001). However, no such relationship could be observed for MEFV genotypic subgroups M694V/Other (p=0.465) and Other/Other (p=0.697). Conclusion. Our data suggest, that the influence of SAA1 genotypic variation on the age of disease onset restricts to FMF patients homozygous for MEFV mutation M694V.

Automated summary

The study showed a significant association between the SAA1 genotype beta/beta and delayed disease onset in M694V homozygous FMF patients. However, this relationship was not observed in patients with other MEFV genotypes.