Ozone, oxidant defense genes, and risk of asthma during adolescence
Ozone, oxidant defense genes, and risk of asthma during adolescence
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DOI：
10.1164/rccm.200706-863oc
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发表时间：
2008-02-15
影响因子：
24.7
通讯作者：
Gilliland, Frank D.
中科院分区：
文献类型：
--
作者：
Islam, Talat;McConnell, Rob;Gilliland, Frank D.
基本原理：虽然氧化应激是哮喘的主要特征，但氧化性空气污染物和抗氧化基因血红素氧合酶1（HMOX-1）、过氧化氢酶（CAT）和锰超氧化物歧化酶（MNSOD）在哮喘发病机制中的作用尚未确定。我们假设HMOX-1（[GT]（n）repeat）、CAT和CAT的功能多态性可能与HMOX-1基因的多态性有关。（-262 C> T-844 C> T）和MNSOD（Ala-9Val）与新发哮喘相关，这些变异体的影响因暴露于臭氧（一种强氧化剂空气污染物）而异。我们在一个基于人群的非西班牙裔队列中评估了这一假设。（n = 11，1125）和西班牙裔白色（n = 586）儿童，他们居住在12个加州社区，每年随访8年以确定新发哮喘。在8年的研究随访期间，对每个研究社区的空气污染物进行了连续测量。HMOX-1“短”等位基因（< 23个重复）与非西班牙裔白人新发哮喘风险降低相关（风险比[HR]，0.64; 95%置信区间[CI]，0.41-0.99）。这种保护作用在居住在低臭氧社区的儿童中最大（HR，0.48; 95% CI，0.25-0.91）（交互作用P值= 0.003）。在西班牙裔儿童中观察到与HMOX-1相关的证据很少。相反，携带CAT-262“T”等位基因变异（CT或TT）的西班牙裔儿童患哮喘的风险增加（HR，1.78; P值= 0.01）。这些多态性的影响没有修改个人吸烟或二手烟exposition.Conclusions：CAT和HMOX-1的功能性启动子变体表现出种族特异性协会与新发哮喘。氧化基因保护仅限于生活在低臭氧社区的儿童。
Rationale: Although oxidative stress is a cardinal feature of asthma, the roles of oxidant air pollutants and antioxidant genes heme oxygenase 1 (HMOX-1), catalase (CAT), and manganese superoxide dismutase (MNSOD) in asthma pathogenesis have yet to be determined.Objectives: We hypothesized that the functional polymorphisms of HMOX-1 ([GT](n) repeat), CAT (-262C > T -844C > T), and MNSOD (Ala-9Val) are associated with new-onset asthma, and the effects of these variants vary by exposure to ozone, a potent oxidant air pollutant.Methods: We assessed this hypothesis in a population-based cohort of non-Hispanic (n = 11,1125) and Hispanic white (n = 586) children who resided in 12 California communities and who were followed annually for 8 years to ascertain new-onset asthma.Measurements and Main Results: Air pollutants were continuously measured in each of the study communities during the 8 years of study follow-up. HMOX-1 "short" alleles (< 23 repeats) were associated with a reduced risk for new-onset asthma among non-Hispanic whites (hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.41-0.99). This protective effect was largest in children residing in low-ozone communities (HR, 0.48; 95% CI, 0.25-0.91) (interaction Pvalue = 0.003). Little evidence for an association with HMOX-1 was observed among Hispanic children. In contrast, Hispanic children with a variant of the CAT-262 "T" allele (CT or TT) had an increased risk for asthma (H R, 1.78; P value = 0.01). The effects of these polymorphisms were not modified by personal smoking or secondhand-smoke exposure.Conclusions: Functional promoter variants in CAT and HMOX-1 showed ethnicity-specific associations with new-onset asthma. Oxidant gene protection was restricted to children living in low-ozone communities.