吸烟、水果和蔬菜摄入能修正过氧化氢酶基因-21A>T的多态性与支气管哮喘风险之间的相关性
2009/06/26
虽然氧化应激是支气管哮喘的主要特征，但环境中的氧化物/抗氧化物暴露与抗氧化物基因之间的相互作用在哮喘发病过程中的作用尚不明确。
在俄罗斯人群中研究过氧化氢酶（CAT）基因的两个常见多态性（-21A > T 和-262C > T）与哮喘易感性之间的关系，并验证有CAT基因型参与的哮喘风险取决于氧化物（吸烟）和抗氧化物（水果和蔬菜的摄入）的暴露水平。在俄罗斯中部选取429名不相关人群，其中包括215名哮喘患者和214名性别、年龄相匹配的健康对照人群。哮喘患者CAT两个等位基因：-21A （OR为0.73；95%CI 0.55-0.96；P= 0.03）和-21AA（OR为0.42；95%CI 0.23-0.76；P= 0.004）的基因多态性频率显著高于健康对照人群。与对照组相比，过敏性哮喘患者（OR 为0.47；95%CI：0.25-0.92；P= 0.024)和非过敏性哮喘患者（OR为0.32；95% CI：0.14-0.71；P = 0.004）CAT 基因的-21AA基因型多态性频率显著高于对照人群（Bonferroni校正P值小于0.025）。CAT基因-21A > T和-262C> T 的基因多态性存在正连锁不平衡（P < 0.0001）。有-21AA 基因型的吸烟者患非过敏性哮喘的风险增加（P = 0.002），但携带该基因型的非吸烟者未见患两种哮喘亚型的风险。值得注意的是，含有CAT 基因型-21AA 的哮喘患者与高水果、蔬菜摄入无相关性，但含该基因型的低水果、蔬菜摄入人群（每天1次或更少）患过敏性（P = 0.013）和非过敏性哮喘的风险增加（P = 0.008）。
本文为首次报道CAT基因-21A > T基因多态性与过敏性和非过敏性哮喘相关的研究。我们首次发现，对于携带有-21AA基因型的人群，吸烟和水果或蔬菜的摄入对其患哮喘的风险的影响为反向修正，而且基因与环境因素相互作用的结果也支持CAT基因与支气管哮喘相关。
在俄罗斯人群中研究过氧化氢酶（CAT）基因的两个常见多态性（-21A > T 和-262C > T）与哮喘易感性之间的关系，并验证有CAT基因型参与的哮喘风险取决于氧化物（吸烟）和抗氧化物（水果和蔬菜的摄入）的暴露水平。在俄罗斯中部选取429名不相关人群，其中包括215名哮喘患者和214名性别、年龄相匹配的健康对照人群。哮喘患者CAT两个等位基因：-21A （OR为0.73；95%CI 0.55-0.96；P= 0.03）和-21AA（OR为0.42；95%CI 0.23-0.76；P= 0.004）的基因多态性频率显著高于健康对照人群。与对照组相比，过敏性哮喘患者（OR 为0.47；95%CI：0.25-0.92；P= 0.024)和非过敏性哮喘患者（OR为0.32；95% CI：0.14-0.71；P = 0.004）CAT 基因的-21AA基因型多态性频率显著高于对照人群（Bonferroni校正P值小于0.025）。CAT基因-21A > T和-262C> T 的基因多态性存在正连锁不平衡（P < 0.0001）。有-21AA 基因型的吸烟者患非过敏性哮喘的风险增加（P = 0.002），但携带该基因型的非吸烟者未见患两种哮喘亚型的风险。值得注意的是，含有CAT 基因型-21AA 的哮喘患者与高水果、蔬菜摄入无相关性，但含该基因型的低水果、蔬菜摄入人群（每天1次或更少）患过敏性（P = 0.013）和非过敏性哮喘的风险增加（P = 0.008）。
本文为首次报道CAT基因-21A > T基因多态性与过敏性和非过敏性哮喘相关的研究。我们首次发现，对于携带有-21AA基因型的人群，吸烟和水果或蔬菜的摄入对其患哮喘的风险的影响为反向修正，而且基因与环境因素相互作用的结果也支持CAT基因与支气管哮喘相关。
（陈欣 审校）
Polonikov AV, et al. J Asthma. 2009 Apr;46(3):217-224
Tobacco smoking, fruit and vegetable intake modify association between -21A>T polymorphism of catalase gene and risk of bronchial asthma.
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.
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