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.
Lingua originale | English |
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pagine (da-a) | 162-168 |
Numero di pagine | 7 |
Rivista | Pharmacogenomics Journal |
Volume | 8 |
DOI | |
Stato di pubblicazione | Pubblicato - 2008 |
Keywords
- Adult
- Anti-Bacterial Agents
- Case-Control Studies
- Drug Hypersensitivity
- Female
- Gene Frequency
- Genetic Predisposition to Disease
- Haplotypes
- Humans
- Immunoglobulin E
- Italy
- Male
- Middle Aged
- Odds Ratio
- Phenotype
- Polymorphism, Genetic
- Prospective Studies
- Risk Assessment
- Risk Factors
- Severity of Illness Index
- Skin Tests
- Tumor Necrosis Factor-alpha
- beta-Lactams