Tobacco Smoking, Fruit and Vegetable Intake Modify Association Between-21A T Polymorphism of Catalase Gene and Risk of Bronchial Asthma
Tobacco Smoking, Fruit and Vegetable Intake Modify Association Between-21A T Polymorphism of Catalase Gene and Risk of Bronchial Asthma
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DOI：
10.1080/02770900802492103
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发表时间：
2009-01-01
影响因子：
1.9
通讯作者：
Panfilov, V. I.
中科院分区：
文献类型：
--
作者：
Polonikov, A. V.;Ivanov, V. P.;Panfilov, V. I.
尽管氧化应激是支气管哮喘的一个主要特征，但环境氧化剂/抗氧化剂暴露与抗氧化基因之间的相互作用在哮喘病因学中的作用尚未确定。本研究旨在调查过氧化氢酶（CAT）基因的两个常见多态性-21A T和-262C T是否与俄罗斯人群的哮喘易感性相关，并检验CAT基因型导致的哮喘风险可能取决于氧化剂（吸烟）和抗氧化剂（水果和蔬菜摄入）暴露的假设。该研究共招募了 429 名来自俄罗斯中部的无关俄罗斯人，其中包括 215 名哮喘患者和 214 名性别和年龄匹配的健康对照者。通过 PCR-RFLP 分析对 CAT 基因多态性进行基因分型分析。哮喘患者中等位基因-21A（OR 0.73 95%CI 0.55-0.96 p = 0.03）和-21AA CAT基因型（OR 0.42 95%CI 0.23-0.76 p = 0.004）的频率均高于健康对照者。与对照组相比（Bonferroni 校正 p 值小于 0.025），过敏性哮喘患者 (OR 0.47 95%CI 0.25-0.92 p = 0.024) 和非过敏性哮喘患者 (OR 0.32 95%CI 0.14-0.71 p = 0.004) CAT 基因 -21AA 基因型频率显着较高。过氧化氢酶基因的-21A T 和-262C T 多态性呈正连锁不平衡(p < 0.0001)。携带-21AA基因型的吸烟者患非过敏性哮喘的风险增加（p = 0.002），而携带该基因型的非吸烟者则没有患该疾病任何变异的风险。值得注意的是，在水果和蔬菜摄入量较高的人群中，未发现 CAT 基因型 -21AA 与哮喘相关，而具有该基因型的水果和蔬菜摄入量较低（每天一次或更少）的患者患过敏性哮喘（p = 0.013）和非过敏性哮喘（p = 0.008）的风险增加。这是第一项报告过氧化氢酶基因多态性-21A T 与过敏性和非过敏性哮喘相关的研究。我们还首次发现，吸烟和水果和蔬菜摄入量对 -21AA CAT 基因型个体的哮喘风险具有潜在的反向影响，并且发现的基因-环境相互作用支持过氧化氢酶基因与支气管哮喘发展的生物学合理性。
Although oxidative stress is a cardinal feature of bronchial asthma, the role of interactions between environmental oxidant/antioxidant exposures and antioxidant genes in asthma aetiology has yet to be determined. The present study was conducted to investigate whether two common polymorphisms -21A T and -262C T of catalase (CAT) gene are associated with susceptibility to asthma in a Russian population and to test the hypothesis that the asthma risk attributed to CAT genotypes could be dependent on both oxidant (tobacco smoking) and antioxidant (fruit and vegetable intake) exposures. A total of 429 unrelated Russian individuals from Central Russia were recruited in the study, including 215 asthmatics and 214 sex- and age-matched healthy controls. Genotyping analysis for the CAT gene polymorphisms was performed by PCR-RFLP assays. The frequencies of both allele -21A (OR 0.73 95%CI 0.55-0.96 p = 0.03) and -21AA CAT genotype (OR 0.42 95%CI 0.23-0.76 p = 0.004) were higher among asthmatics than among healthy controls. The frequency of -21AA genotype of the CAT gene was significantly higher in patients with allergic (OR 0.47 95%CI 0.25-0.92 p = 0.024) and nonallergic (OR 0.32 95%CI 0.14-0.71 p = 0.004) asthma in comparison with controls (at the Bonferroni corrected p value less than 0.025). Polymorphisms -21A T and -262C T of the catalase gene were in a positive linkage disequilibrium (p 0.0001). Smokers who carried -21AA genotype had an increased risk of nonallergic asthma (p = 0.002), whereas nonsmoker carriers of this genotype did not have the risk of any variant of the disease. Notably, no association of CAT genotype -21AA with asthma was found in high fruit and vegetable consumers, whereas low fruit and vegetable consumers (one time per day or less often) possessing this genotype were at increased risk of both allergic (p = 0.013) and nonallergic (p = 0.008) asthma. This is the first study reporting an association of polymorphism -21A T of the catalase gene with allergic and nonallergic asthma. We also found, for the first time, that cigarette smoking and fruit and vegetable intakes have potentially inverse modifying influences on the asthma risk in individuals with -21AA CAT genotype and that the gene-environment interactions that were found support the biologic plausibility of catalase gene for the development of bronchial asthma.