Novel candidate genes important for asthma and hypertension comorbidity revealed from associative gene networks

Abstract

Background: Hypertension and bronchial asthma are a major issue for people's health. As of 2014, approximately one billion adults, or~22% of the world population, have had hypertension. As of 2011, 235-330 million people globally have been affected by asthma and approximately 250,000-345,000 people have died each year from the disease. The development of the effective treatment therapies against these diseases is complicated by their comorbidity features. This is often a major problem in diagnosis and their treatment. Hence, in this study the bioinformatical methodology for the analysis of the comorbidity of these two diseases have been developed. As such, the search for candidate genes related to the comorbid conditions of asthma and hypertension can help in elucidating the molecular mechanisms underlying the comorbid condition of these two diseases, and can also be useful for genotyping and identifying new drug targets. Results: Using ANDSystem, the reconstruction and analysis of gene networks associated with asthma and hypertension was carried out. The gene network of asthma included 755 genes/proteins and 62,603 interactions, while the gene network of hypertension -713 genes/proteins and 45,479 interactions. Two hundred and five genes/proteins and 9638 interactions were shared between asthma and hypertension. An approach for ranking genes implicated in the comorbid condition of two diseases was proposed. The approach is based on nine criteria for ranking genes by their importance, including standard methods of gene prioritization (Endeavor, ToppGene) as well as original criteria that take into account the characteristics of an associative gene network and the presence of known polymorphisms in the analysed genes. According to the proposed approach, the genes IL10, TLR4, and CAT had the highest priority in the development of comorbidity of these two diseases. Additionally, it was revealed that the list of top genes is enriched with apoptotic genes and genes involved in biological processes related to the functioning of central nervous system.

Recent findings in the genetics and epigenetics of asthma and allergy

“…In large twin populations from Scandinavia, genetic traits for asthma overlapped with those from different affective disorders such as major depression disorder, primary anxiety disorder, and most of all, neuroticism [16]. Using sophisticated bioinformatics tools, also an overlap between gene networks contributing to asthma and hypertension based on genetic databases and bioinformatic ranking algorithms was identified [17]. The genes most likely in the center of the asthma and hypertension interaction were IL10, TLR4, and CAT, suggesting that mechanisms of adaptive and innate immunity are shared in the development of both diseases.…”

Gene network analysis of complex diseases using GenCoNet

“…GenCoNet is meant to be a qualitative resource that facilitates researchers access the relevant information. Our study [1] showed that the application of methods of reconstruction and analysis of gene networks is a productive tool to rank candidate genes by their importance to complex diseases (e.g. asthma and hypertension).…”

Il17a Genetic / F Polymorphism in Bronchial Asthma Pathogenesis in Children

“…Поддерживая эти наблюдения, функциональный анализ показал, что IL-17A и IL-17F способны стимулировать бронхиальные фибробласты, эпителиальные клетки и клетки гладкой мускулатуры и вызывать экспрессию различных цитокинов и хемокинов, включая IL-8, IL-6, IL-11 и CXCL1, которые важны для гранулопоэза и нейтрофилов [15]. Способность IL-17A и IL-17F индуцировать миграцию нейтрофилов предполагает, что они участвуют в патогенезе тяжелой формы БА, основной характеристикой которой является нейтрофильное воспаление в дыхательных путях [14,15] Генетические исследования полиморфных генов могут служить способом, помогающим продемонстрировать связи между определенными белками и БА, характеризующиеся взаимодействием нескольких генов в разных хромосомах [3,14,17,18]. Гены, кодирующие семейство IL-17, расположены на 6q12 хромосоме, при множественном сканировании генома показано, что это геномная область, связанная с определенными фенотипами БА [19].…”