Association of tumor necrosis factor-α-308G>A polymorphism with IgE-mediated allergy to betalactams in an Italian population
Association of tumor necrosis factor-α-308G>A polymorphism with IgE-mediated allergy to betalactams in an Italian population
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DOI：
10.1038/sj.tpj.6500456
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发表时间：
2008-04-01
影响因子：
2.8
通讯作者：
Romano, A.
中科院分区：
文献类型：
--
作者：
Gueant-Rodriguez, R-M;Gueant, J-L;Romano, A.
肿瘤坏死因子-α（TNF-α）通过免疫球蛋白E（IgE）依赖性机制从肥大细胞释放。TNFA基因-308位点G > A变异是HLA-A1-B8-DR 3-DQ 2扩展单倍型的一部分，影响基因表达。我们在427名受试者中评估了这种变异与IgE介导的β-内酰胺类药物反应的关系，包括167例病例和260例年龄和性别配对的对照。TNFA GG基因型与总IgE水平同时是β内酰胺过敏主要风险的显著独立预测因子，年龄和性别校正比值比估计为2.45（95%置信区间：1.18-5.08，P = 0.0163）。-308AA基因型患者血清特异性IgE水平显著高于-308GA/GG基因型患者，其中位数（相对单位）分别为4.6（四分位数：3.9-10.6）和2.2（1.4-4.3）（P = 0.0046）。总之，我们的研究结果表明，促炎途径的遗传决定因素对IgE介导的β-内酰胺类药物超敏反应具有矛盾的影响。
Tumor necrosis factor-a ( 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.