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

Abstract

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.

• Authors: José-Noel Ibrahim, Eliane Chouery, Jean-Claude Lecron, André Mégarbané, Myrna Medlej-Hashim
• Journal: European journal of medical genetics (Eur J Med Genet) Vol. 58 Issue 12 Pg. 668-73 (Dec 2015) ISSN: 1878-0849 [Electronic] Netherlands
• PMID: 26585190 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Chemical References

• Interleukin 1 Receptor Antagonist Protein
• Interleukin-1beta
• Colchicine

Topics

• Adult
• Alleles
• Amino Acid Substitution
• Case-Control Studies
• Colchicine (therapeutic use)
• Familial Mediterranean Fever (diagnosis, drug therapy, genetics)
• Female
• Genetic Association Studies
• Genetic Predisposition to Disease
• Genotype
• Humans
• Interleukin 1 Receptor Antagonist Protein (genetics)
• Interleukin-1beta (genetics)
• Male
• Minisatellite Repeats
• Phenotype
• Polymorphism, Single Nucleotide
• Severity of Illness Index
• Young Adult