Study of the association of IL-1β and IL-1RA gene polymorphisms with occurrence and severity of Familial Mediterranean fever

Familial Mediterranean fever (FMF) is a recessive autoinflammatory disorder. The balance between the pro-inflammatory cytokine IL-1β and its receptor antagonist IL-1RA plays an important role in the development of FMF. In order to determine a possible association of polymorphisms in IL-1β and IL-1RA genes with occurrence and/or severity of the disease, 42 genetically confirmed FMF patients and 42 controls were genotyped for IL-1β(−511C/T), IL-1β(−31T/C), IL1-1β(+3954T/C) and IL-1RA VNTR polymorphisms. IL-1β and IL-1RA levels were evaluated by multiplex ELISA in supernatants of PBMC cultures of 30 FMF patients with and without 24h stimulation of monocytes by LPS. The CC genotype and C allele at positions −31 and + 3954 of IL-1β gene were more frequent in FMF patients than in controls. FMF patients carriers of IL-1β(−31) CC genotype were associated with a 2-fold increase in LPS-induced IL-1β secretion as well as a higher disease severity score (11.2 ± 2.9) when compared to patients carrying the TC and TT genotypes (6.1 ± 2.1 and 4.5 ± 2.4, respectively). These results indicate that IL-1β gene polymorphisms at positions −31 and + 3954 may be associated with an increased risk for FMF. IL-1β(−31) contributes also to the severity of the disease, probably by modulating IL-1β synthesis.