Antioxidant Defense Enzyme Genes and Asthma Susceptibility: Gender-Specific Effects and Heterogeneity in Gene-Gene Interactions between Pathogenetic Variants of the Disease

Author:

Polonikov Alexey V.1,Ivanov Vladimir P.1,Bogomazov Alexey D.2,Freidin Maxim B.3,Illig Thomas45,Solodilova Maria A.1

Affiliation:

1. Department of Biology, Medical Genetics and Ecology, Kursk State Medical University, 3 Karl Marx Street, Kursk 305041, Russia

2. Department of Pediatrics, Kursk State Medical University, 11a Koltsov Street, Kursk 305035, Russia

3. Research Institute for Medical Genetics, Siberian Branch of Russian Academy of Medical Sciences, 10 Nabereznaya Ushaiki Tomsk 634050, Russia

4. Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany

5. Hanover Unified Biobank, Hanover Medical School, Carl-Neuberg-Strasse 1, 30625 Hanover, Germany

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 identifiedGSR(glutathione reductase) andPON2(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.

Funder

Federal Targeted Program “Scientific and Scientific-Pedagogical Personnel of the Innovative Russia in 2009–2013.”

Publisher

Hindawi Limited

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3