Nicotinamide adenine dinucleotide (phosphate) reduced: Quinone oxidoreductase and glutathione S-transferase M1 polymorphisms and childhood asthma
Nicotinamide adenine dinucleotide (phosphate) reduced: Quinone oxidoreductase and glutathione S-transferase M1 polymorphisms and childhood asthma
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DOI：
10.1164/rccm.200305-684oc
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发表时间：
2003-11-15
影响因子：
24.7
通讯作者：
London, SJ
中科院分区：
文献类型：
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作者：
David, GL;Romieu, I;London, SJ
烟酰胺腺嘌呤二核苷酸(磷酸)还原：苯醌氧化还原酶(NQO1)和谷胱甘肽S转移酶(GST)M1是11相酶，对氧化应激反应非常重要，如暴露在臭氧中。我们研究了NQO1(Prol187Ser)和GSTM1(纯合缺失)功能显著多态与终生高臭氧暴露儿童哮喘风险的关系。我们从墨西哥城一家公立儿科医院的过敏转诊诊所招募了患有哮喘的儿童，以及他们的父母。我们采用聚合酶链式反应-限制性片段长度多态性分析方法检测了218例家族性三联症患者的NQO1基因Pro187Ser多态性，并用聚合酶链式反应方法检测了GSTM1基因的存在。我们没有发现NQO1基因单独与哮喘风险相关的有力证据。然而，在GSTM1纯合子缺失的受试者中，与Pro/Pro纯合子相比，丝氨酸等位基因携带者患哮喘的风险显著降低(相对风险=0.4；95%可信区间0.2-0.8)。GSTM1型与NQO1型的相对危险度差异p值=0.013。这些数据与NQO1Ser等位基因在高臭氧暴露的GSTM1缺失儿童群体中的保护作用是一致的。
Nicotinamide adenine dinucleotide (phosphate) reduced:quinone oxidoreductase (NQO1) and glutathione S-transferase (GST) M1 are phase 11 enzymes important in response to oxidative stress, such as occurs during exposure to ozone. We examined the relationship between functionally significant polymorphisms in NQO1 (Prol187Ser) and GSTM1 (homozygous deletion) and asthma risk in children with high lifetime exposure to ozone. We enrolled children with asthma from the allergy referral clinic at a public pediatric hospital in Mexico City, together with their parents. We assayed for the Pro187Ser polymorphism in NQO1 using a polymerase chain reaction-restriction fragment length polymorphism assay and for the presence of GSTM1 by polymerase chain reaction among 218 case-parent triads. We did not find strong evidence of an association between NQO1 genotype alone and asthma risk. However, among subjects with homozygous deletion of GSTM1, carriers of a serine allele were at significantly reduced risk of asthma compared with Pro/Pro homozygotes (relative risk = 0.4; 95% confidence interval, 0.2-0.8). The p value for difference in relative risk for NQO1 by GSTM1 genotype = 0.013. These data are consistent with a protective effect of the NQO1 Ser allele in this population of GSTM1-null children with high ozone exposure.