title: Antioxidant defense enzyme genes and asthma susceptibility: gender-specific effects and heterogeneity in gene-gene interactions between pathogenetic variants of the disease.
abstract: 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.
authors.affiliation: Department of Biology, Medical Genetics and Ecology, Kursk State Medical University, 3 Karl Marx Street, Kursk 305041, Russia.
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Polonikov
authors.affiliation: Department of Biology, Medical Genetics and Ecology, Kursk State Medical University, 3 Karl Marx Street, Kursk 305041, Russia.
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Ivanov
authors.affiliation: Department of Pediatrics, Kursk State Medical University, 11a Koltsov Street, Kursk 305035, Russia.
authors.forename: Alexey D
authors.initials: AD
authors.lastname: Bogomazov
authors.affiliation: Research Institute for Medical Genetics, Siberian Branch of Russian Academy of Medical Sciences, 10 Nabereznaya Ushaiki Tomsk 634050, Russia.
authors.forename: Maxim B
authors.initials: MB
authors.lastname: Freidin
authors.affiliation: Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany ; Hanover Unified Biobank, Hanover Medical School, Carl-Neuberg-Strasse 1, 30625 Hanover, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.affiliation: Department of Biology, Medical Genetics and Ecology, Kursk State Medical University, 3 Karl Marx Street, Kursk 305041, Russia.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Solodilova
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000378:metabolism*; D001249:Asthma / Q000201:enzymology* / Q000235:genetics*; D016022:Case-Control Studies; D004843:Epistasis, Genetic; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D018740:Genetic Heterogeneity; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D058011:Multifactor Dimensionality Reduction; D010084:Oxidation-Reduction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D012727:Sex Characteristics; D013223:Statistics as Topic; D055815:Young Adult
chemical_list: D000975:Antioxidants