谷胱甘肽-S-转移酶M1和P1基因型对异生物素增强过敏反应的影响：随机、安慰剂对照交叉研究。
Effect of glutathione-S-transferase M1 and P1 genotypes on xenobiotic enhancement of allergic responses: randomised, placebo-controlled crossover study.
作者信息
Gilliland Frank D, Li Yu-Fen, Saxon Andrew, Diaz-Sanchez David
机构信息
Department of Preventive Medicine, University of Southern California, Keck School of Medicine, Los Angeles, CA 90033, USA.
出版信息
Lancet. 2004 Jan 10;363(9403):119-25. doi: 10.1016/S0140-6736(03)15262-2.
BACKGROUND
Particulate pollution is associated with the occurrence of asthma and allergy. The model pollutant, diesel exhaust particles, can participate with allergens in starting and exacerbating allergic airway diseases in part by production of reactive oxygen species. Glutathione-S-transferases (GSTs) can metabolise reactive oxygen species and detoxify xenobiotics present in diesel exhaust particles. We tested the hypothesis that null genotypes for GSTM1 and GSTT1, and GSTP1 codon 105 variants (I105 and V105) are key regulators of the adjuvant effects of diesel exhaust particles on allergic responses.
METHODS
Patients sensitive to the ragweed allergen were challenged intranasally with allergen alone and with allergen plus diesel exhaust particles in a randomised order at separate visits. Nasal allergen-specific IgE, histamine, interleukin 4, and interferon gamma concentrations were measured before and 24 h after challenge.
FINDINGS
Individuals with GSTM1 null or the GSTP1 I105 wildtype genotypes showed enhanced nasal allergic responses in the presence of diesel exhaust particles. Compared with patients with a functional GSTM1 genotype, GSTM1 null patients had a significantly larger increase in IgE (median 102.5 U/mL [range 1.0-510.5] vs 45.5 U/mL [1.5-60.6], p=0.03) and histamine (14.0 nmol/L [-0.2-24.7] vs 7.4 nmol/L [1.2-12.3], p=0.02) after diesel exhaust particles plus allergen challenge. The I105 GSTP1 genotype was associated with an increase in IgE (120.3 U/mL [6.7-510.5] vs 27.7 U/mL [-1.5-60.6], p=0.03) and histamine (13.8 nmol/L [3.1-24.7] vs 5.2 nmol/L [-0.2-19.6], p=0.01) after challenge with diesel exhaust particles and allergens. The diesel exhaust particles enhancement was largest in patients with both the GSTM1 null and GSTP1 I/I genotypes.
INTERPRETATION
GSTM1 and GSTP1 modify the adjuvant effect of diesel exhaust particles on allergic inflammation.
背景
颗粒物污染与哮喘和过敏的发生有关。典型污染物柴油废气颗粒可通过产生活性氧，与过敏原共同引发和加剧过敏性气道疾病。谷胱甘肽-S-转移酶（GSTs）可代谢活性氧并使柴油废气颗粒中的外源性物质解毒。我们检验了以下假设：GSTM1和GSTT1的无效基因型以及GSTP1密码子105变体（I105和V105）是柴油废气颗粒对过敏反应辅助作用的关键调节因子。
方法
对豚草过敏原敏感的患者在不同就诊时按随机顺序分别接受单独过敏原鼻内激发以及过敏原加柴油废气颗粒的鼻内激发。在激发前和激发后24小时测量鼻内过敏原特异性IgE、组胺、白细胞介素4和干扰素γ浓度。
结果
GSTM1无效或GSTP1 I105野生型基因型个体在存在柴油废气颗粒的情况下表现出增强的鼻内过敏反应。与具有功能性GSTM1基因型的患者相比，GSTM1无效的患者在柴油废气颗粒加过敏原激发后，IgE（中位数102.5 U/mL [范围1.0 - 510.5] 对45.5 U/mL [1.5 - 60.6]，p = 0.03）和组胺（14.0 nmol/L [-0.2 - 24.7] 对7.4 nmol/L [1.2 - 12.3]，p = 0.02）有显著更大的增加。GSTP1 I105基因型与柴油废气颗粒和过敏原激发后IgE（120.3 U/mL [6.7 - 510.5] 对27.7 U/mL [-1.5 - 60.6]，p = 0.03）和组胺（13.8 nmol/L [3.1 - 24.7] 对5.2 nmol/L [-0.2 - 19.6]，p = 0.01）的增加相关。在同时具有GSTM1无效和GSTP1 I/I基因型的患者中，柴油废气颗粒的增强作用最大。
解读
GSTM1和GSTP1改变了柴油废气颗粒对过敏性炎症的辅助作用。
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