Polonikov Alexey V, Ivanov Vladimir P, Bogomazov Alexey D, Freidin Maxim B, Illig Thomas, Solodilova Maria A
Department of Biology, Medical Genetics and Ecology, Kursk State Medical University, 3 Karl Marx Street, Kursk 305041, Russia.
Department of Pediatrics, Kursk State Medical University, 11a Koltsov Street, Kursk 305035, Russia.
Biomed Res Int. 2014;2014:708903. doi: 10.1155/2014/708903. Epub 2014 May 5.
Oxidative stress resulting from an increased amount of reactive oxygen species and an imbalance between oxidants and antioxidants plays an important role in the pathogenesis of asthma. The present study tested the hypothesis that genetic susceptibility to allergic and nonallergic variants of asthma is determined by complex interactions between genes encoding antioxidant defense enzymes (ADE). We carried out a comprehensive analysis of the associations between adult asthma and 46 single nucleotide polymorphisms of 34 ADE genes and 12 other candidate genes of asthma in Russian population using set association analysis and multifactor dimensionality reduction approaches. We found for the first time epistatic interactions between ADE genes underlying asthma susceptibility and the genetic heterogeneity between allergic and nonallergic variants of the disease. We identified GSR (glutathione reductase) and PON2 (paraoxonase 2) as novel candidate genes for asthma susceptibility. We observed gender-specific effects of ADE genes on the risk of asthma. The results of the study demonstrate complexity and diversity of interactions between genes involved in oxidative stress underlying susceptibility to allergic and nonallergic asthma.
活性氧种类数量增加以及氧化剂与抗氧化剂之间失衡所导致的氧化应激在哮喘发病机制中起重要作用。本研究检验了以下假设：哮喘的过敏性和非过敏性变体的遗传易感性由编码抗氧化防御酶（ADE）的基因之间的复杂相互作用决定。我们使用集合关联分析和多因素降维方法，对俄罗斯人群中成人哮喘与34个ADE基因的46个单核苷酸多态性以及12个其他哮喘候选基因之间的关联进行了全面分析。我们首次发现了哮喘易感性潜在的ADE基因之间的上位性相互作用以及该疾病过敏性和非过敏性变体之间的遗传异质性。我们确定谷胱甘肽还原酶（GSR）和对氧磷酶2（PON2）为哮喘易感性的新候选基因。我们观察到ADE基因对哮喘风险存在性别特异性影响。该研究结果证明了参与氧化应激的基因之间相互作用的复杂性和多样性，这些基因与过敏性和非过敏性哮喘的易感性相关。
