Center for Environmental Medicine, Asthma and Lung Biology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7310, USA.
Occup Environ Med. 2011 Oct;68(10):783-5. doi: 10.1136/oem.2010.061747. Epub 2011 Mar 25.
To determine if the GSTM1 null genotype is a risk factor for increased inflammatory response to inhaled endotoxin.
35 volunteers who had undergone inhalation challenge with a 20 000 endotoxin unit dose of Clinical Center Reference Endotoxin (CCRE) were genotyped for the GSTM1 null polymorphism. Parameters of airway and systemic inflammation observed before and after challenge were compared in GSTM1 null (n=17) and GSTM1 (n=18) sufficient volunteers.
GSTM1 null volunteers had significantly increased circulating white blood cells (WBCs), polymorphonuclear neutrophils (PMNs), platelets and sputum PMNs (% sputum PMNs and PMNs/mg sputum) after CCRE challenge. GSTM1 sufficient volunteers had significant, but lower increases in circulating WBCs, PMNs and % sputum PMNs, and no increase in platelets or PMNs/mg sputum. Linear regression analysis adjusted for baseline values of the entire cohort revealed that the GSTM1 null genotype significantly increased circulating WBCs, platelets and % sputum PMNs after challenge.
These data support the hypothesis that the GSTM1 null genotype is a risk factor for increased acute respiratory and systemic inflammatory response to inhaled CCRE. These data are consistent with other observations that the GSTM1 null genotype is associated with increased respiratory, systemic and cardiovascular effects linked to ambient air particulate matter exposure and indicate that the GSTM1 null genotype should be considered a risk factor for adverse health effects associated with exposure to environmental endotoxin.
确定 GSTM1 无效基因型是否是对吸入内毒素产生过度炎症反应的危险因素。
35 名志愿者接受了 20000 单位临床中心参考内毒素（CCRE）剂量的吸入挑战，对 GSTM1 无效多态性进行了基因分型。在 GSTM1 无效（n=17）和 GSTM1 （n=18）充足的志愿者中，比较了挑战前后气道和全身炎症的参数。
CCRE 挑战后，GSTM1 无效志愿者的循环白细胞（WBC）、多形核中性粒细胞（PMN）、血小板和痰 PMN（%痰 PMN 和 PMN/mg 痰）显著增加。GSTM1 充足的志愿者循环 WBC、PMN 和%痰 PMN 显著增加，但增加幅度较低，血小板或 PMN/mg 痰无增加。对整个队列的基线值进行线性回归分析显示，GSTM1 无效基因型在挑战后显著增加循环 WBC、血小板和%痰 PMN。
这些数据支持 GSTM1 无效基因型是对吸入 CCRE 产生过度急性呼吸和全身炎症反应的危险因素的假设。这些数据与其他观察结果一致，即 GSTM1 无效基因型与与环境空气中颗粒物暴露相关的呼吸、全身和心血管影响增加有关，并表明 GSTM1 无效基因型应被视为与暴露于环境内毒素相关的不良健康影响的危险因素。
