title: 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.affiliation: ER030-EDST, Department of Life and Earth Sciences, Faculty of Sciences II, Lebanese University, Lebanon; Laboratoire Inflammation, Tissus Epithéliaux et Cytokines (LITEC), EA4331, University and Hospital of Poitiers, France.
authors.forename: José-Noel
authors.initials: JN
authors.lastname: Ibrahim
authors.affiliation: Medical Genetics Unit, Faculty of Medicine, Saint Joseph University, Lebanon.
authors.forename: Eliane
authors.initials: E
authors.lastname: Chouery
authors.affiliation: Laboratoire Inflammation, Tissus Epithéliaux et Cytokines (LITEC), EA4331, University and Hospital of Poitiers, France.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Lecron
authors.affiliation: Medical Genetics Unit, Faculty of Medicine, Saint Joseph University, Lebanon.
authors.forename: André
authors.initials: A
authors.lastname: Mégarbané
authors.affiliation: ER030-EDST, Department of Life and Earth Sciences, Faculty of Sciences II, Lebanese University, Lebanon. Electronic address: myrnahachem@ul.edu.lb.
authors.forename: Myrna
authors.initials: M
authors.lastname: Medlej-Hashim
mesh_terms: D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution; D016022:Case-Control Studies; D003078:Colchicine / Q000627:therapeutic use; D010505:Familial Mediterranean Fever / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics*; D053583:Interleukin-1beta / Q000235:genetics*; D008297:Male; D018598:Minisatellite Repeats; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D003078:Colchicine
keywords: FMF; IL-1RA; IL-1β; Polymorphisms