title: Association of tumor necrosis factor-alpha -308G>A polymorphism with IgE-mediated allergy to betalactams in an Italian population.
abstract: Tumor necrosis factor-alpha (TNF-alpha) is released from mast cells via an immunoglobulin E (IgE)-dependent mechanism. The variant G>A at -308 of TNFA is part of an extended haplotype HLA-A1-B8-DR3-DQ2 and influences the gene expression. We evaluated this variant in relation to IgE-mediated reactions to betalactams, in 427 subjects, including 167 cases and 260 age- and gender-paired controls. TNFA GG genotype was a significant independent predictor of the primary risk of betalactam allergy, concurrently with total IgE level, with an age- and sex-adjusted odds ratio estimated at 2.45 (95% confidence interval: 1.18-5.08, P=0.0163). Cases with -308AA genotype had a higher serum level of specific IgE than those with -308GA/GG genotype, with median levels (relative units) of 4.6 (inter-quartiles: 3.9-10.6) and 2.2 (1.4-4.3), respectively (P=0.0046). In conclusion, our results suggest an ambivalent influence of a genetic determinant of pro-inflammatory pathways on IgE-mediated hypersensitivity to betalactams.
authors.affiliation: Inserm U-724, Faculté de Médecine, University of Nancy-Henri Poincaré and University Hospital Center (CHU) of Nancy, Nancy, France.
authors.forename: R-M
authors.initials: RM
authors.lastname: Guéant-Rodriguez
authors.forename: J-L
authors.initials: JL
authors.lastname: Guéant
authors.forename: M
authors.initials: M
authors.lastname: Viola
authors.forename: D
authors.initials: D
authors.lastname: Tramoy
authors.forename: F
authors.initials: F
authors.lastname: Gaeta
authors.forename: A
authors.initials: A
authors.lastname: Romano
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000276:immunology; D016022:Case-Control Studies; D004342:Drug Hypersensitivity / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D007558:Italy; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D012882:Skin Tests; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D047090:beta-Lactams / Q000009:adverse effects* / Q000276:immunology
chemical_list: D000900:Anti-Bacterial Agents; D014409:Tumor Necrosis Factor-alpha; D047090:beta-Lactams; D007073:Immunoglobulin E