David Gloria L, Romieu Isabelle, Sienra-Monge Juan Jose, Collins William J, Ramirez-Aguilar Matiana, del Rio-Navarro Blanca Estela, Reyes-Ruiz Norma Isabel, Morris Richard W, Marzec Jacqueline M, London Stephanie J
National Institute of Environmental Health Sciences, PO Box 12233, MD D2-01, Research Triangle Park, NC 27709, USA.
Am J Respir Crit Care Med. 2003 Nov 15;168(10):1199-204. doi: 10.1164/rccm.200305-684OC. Epub 2003 Sep 11.
Nicotinamide adenine dinucleotide (phosphate) reduced:quinone oxidoreductase (NQO1) and glutathione S-transferase (GST) M1 are phase II enzymes important in response to oxidative stress, such as occurs during exposure to ozone. We examined the relationship between functionally significant polymorphisms in NQO1 (Pro187Ser) 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.
还原型烟酰胺腺嘌呤二核苷酸（磷酸）：醌氧化还原酶（NQO1）和谷胱甘肽S-转移酶（GST）M1是Ⅱ相酶，在应对氧化应激（如接触臭氧时发生的氧化应激）中起重要作用。我们研究了NQO1（Pro187Ser）和GSTM1（纯合缺失）功能上显著的多态性与终生高暴露于臭氧的儿童哮喘风险之间的关系。我们从墨西哥城一家公立儿童医院的过敏转诊诊所招募了哮喘儿童及其父母。我们使用聚合酶链反应-限制性片段长度多态性分析法检测了218个病例-父母三联体中NQO1的Pro187Ser多态性，并通过聚合酶链反应检测了GSTM1的存在情况。我们没有发现仅NQO1基因型与哮喘风险之间存在关联的有力证据。然而，在GSTM1纯合缺失的受试者中，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%置信区间，0.2-0.8）。NQO1相对风险因GSTM1基因型而异的p值=0.013。这些数据与NQO1丝氨酸等位基因对该高臭氧暴露的GSTM1缺失儿童群体具有保护作用一致。
