Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan; Research Center for Genes, Environment, and Human Health, College of Public Health, National Taiwan University, Taipei, Taiwan.
Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan.
Chest. 2011 Apr;139(4):839-848. doi: 10.1378/chest.10-2479. Epub 2010 Dec 23.
Epidemiologic studies indicate that exposure to air pollution caused by traffic may have an association with an increased risk of childhood asthma. Some studies report an association between the polymorphisms of the microsomal epoxide hydroxylase (EPHX1) gene and enzyme activity. We investigated the associations of EPHX1 Tyr113His and His139Arg polymorphisms with asthma and wheezing outcomes, and focused on the functional genetic change in different ambient nitrogen dioxide (NO₂) levels on glutathione S-transferase p1 (GSTP1) and glutathione S-transferase m1 (GSTM1) genotypes.
A total of 3,741 children were enrolled in the Taiwan Children Health Study from 14 communities. We examined the associations of EPHX1 Tyr113His and His139Arg genotypes and diplotypes with asthma and wheezing outcomes under different ambient NO₂ exposures.
Children with the EPHX1 Arg/His or Arg/Arg genotypes at codon 139 were significantly associated with increased risks of lifetime asthma (adjusted OR [aOR] = 1.3; 95% CI, 1.1-1.7; and aOR = 1.5; 95% CI, 1.1-2.1, respectively). The EPHX1 diplotypes showed significant associations with lifetime asthma (global P value = .01) and early-onset asthma (global P value = .01). The risk of EPHX1 139Arg allele and 113Tyr-139Arg diplotype were of greater magnitude in higher compared with lower NO₂ communities. The increase of the effect from the EPHX1 139Arg allele with higher NO₂ exposure was most marked in the GSTP1 Val allele and GSTM1 present genotype.
Children with high EPHX1 activity may have increase risk of asthma and wheezing outcomes, and can be mediated through airway oxidative stress generation.
流行病学研究表明，交通造成的空气污染暴露可能与儿童哮喘风险增加有关。一些研究报告称，微粒体环氧化物水解酶（EPHX1）基因的多态性与酶活性之间存在关联。我们调查了 EPHX1 Tyr113His 和 His139Arg 多态性与哮喘和喘息结局之间的关联，并重点关注不同环境二氧化氮（NO₂）水平下谷胱甘肽 S-转移酶 p1（GSTP1）和谷胱甘肽 S-转移酶 m1（GSTM1）基因型的功能遗传变化。
共有 3741 名儿童参与了来自 14 个社区的台湾儿童健康研究。我们检查了 EPHX1 Tyr113His 和 His139Arg 基因型和单体型与不同环境 NO₂暴露下哮喘和喘息结局的关联。
在密码子 139 处具有 EPHX1 Arg/His 或 Arg/Arg 基因型的儿童与终生哮喘的风险显著增加相关（调整后的 OR [aOR] = 1.3；95%CI，1.1-1.7；和 aOR = 1.5；95%CI，1.1-2.1）。EPHX1 单体型与终生哮喘（全局 P 值=.01）和早发哮喘（全局 P 值=.01）具有显著关联。与较低的 NO₂社区相比，EPHX1 139Arg 等位基因和 113Tyr-139Arg 单体型的风险更大。EPHX1 139Arg 等位基因的作用增加与较高的 NO₂暴露的相关性在 GSTP1 Val 等位基因和 GSTM1 存在基因型中最为显著。
EPHX1 活性较高的儿童患哮喘和喘息的风险可能增加，并且可以通过气道氧化应激的产生来介导。
