Islam Talat, McConnell Rob, Gauderman W James, Avol Ed, Peters John M, Gilliland Frank D
M.D. Department of Preventive Medicine, USC Keck School of Medicine, 1540 Alcazar Street, CHP 236, Los Angeles, CA 90033, USA.
Am J Respir Crit Care Med. 2008 Feb 15;177(4):388-95. doi: 10.1164/rccm.200706-863OC. Epub 2007 Nov 29.
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.
We hypothesized that the functional polymorphisms of HMOX-1 (GT 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.
We assessed this hypothesis in a population-based cohort of non-Hispanic (n = 1,125) 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.
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 P value = 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 (HR, 1.78; P value = 0.01). The effects of these polymorphisms were not modified by personal smoking or secondhand-smoke exposure.
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.
尽管氧化应激是哮喘的一个主要特征，但氧化性空气污染物以及抗氧化基因血红素加氧酶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重复序列）、CAT（-262C>T -844C>T）和MNSOD（Ala - 9Val）的功能多态性与新发哮喘有关，并且这些变异的影响因暴露于强效氧化性空气污染物臭氧而有所不同。
我们在一个以人群为基础的队列中评估了这一假设，该队列包括居住在加利福尼亚州12个社区的非西班牙裔（n = 1125）和西班牙裔白人（n = 586）儿童，对他们进行了为期8年的年度随访以确定新发哮喘情况。
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持续测量。HMOX - 1“短”等位基因（<23次重复）与非西班牙裔白人中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为明显（HR，0.48；95%CI，0.25 - 0.91）（交互P值 = 0.003）。在西班牙裔儿童中几乎没有观察到与HMOX - 1相关的证据。相比之下，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）。这些多态性的影响不受个人吸烟或二手烟暴露的影响。
CAT和HMOX - 1中的功能性启动子变异与新发哮喘存在种族特异性关联。氧化基因保护仅限于生活在低臭氧社区的儿童。
