Eczema often precedes the development of asthma in a disease course called the ‘atopic march'. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12 populations including 2,428 cases and 17,034 controls. Here we report two novel loci specific for the combined eczema plus asthma phenotype, which are associated with allergic disease for the first time; rs9357733 located in EFHC1 on chromosome 6p12.3 (OR 1.27; P=2.1 × 10−8) and rs993226 between TMTC2 and SLC6A15 on chromosome 12q21.3 (OR 1.58; P=5.3 × 10−9). Additional susceptibility loci identified at genome-wide significance are FLG (1q21.3), IL4/KIF3A (5q31.1), AP5B1/OVOL1 (11q13.1), C11orf30/LRRC32 (11q13.5) and IKZF3 (17q21). We show that predominantly eczema loci increase the risk for the atopic march. Our findings suggest that eczema may play an important role in the development of asthma after eczema.

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.

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Chlamydia trachomatis infections of the female and male genital tracts are often asymptomatic and, thus, tend to become persistent. In the persistent state the typical Chlamydia life cycle is arrested and standard antibiotic regimens do not always eradicate this infection. We sought to relate treatment failures in men and women with persistent chlamydial genital tract infections to electron microscopic evidence of chlamydial persistence and with atypical morphological forms of the organism. Of 16 patients with chlamydial persistence following azithromycin treatment, morphological variants of this organism were observed by electron microscopy from one endocervical sample and one male urethral sample. We document the presence of intracellular inclusions containing only reticulate bodies, extracellular monomembrane and polymembrane phagosomes containing elementary bodies and reticulate bodies with abnormal outer membranes in the process of dividing extracellularly. These observations parallel previous in vitro studies of chlamydial persistence under adverse conditions. This capacity of C. trachomatis to undergo atypical morphological alterations in vivo may contribute to its persistence and relative resistance to antibiotics.

Co-existence of bronchial asthma (BA) and tuberculosis (TB) is extremely uncommon (dystropic). We assume that this is caused by the interplay between genes involved into specific pathophysiological pathways that arrest simultaneous manifestation of BA and TB. Identification of common and specific genes may be important to determine the molecular genetic mechanisms leading to rare co-occurrence of these diseases and may contribute to the identification of susceptibility genes for each of these dystropic diseases. To address the issue, we propose a new methodological strategy that is based on reconstruction of associative networks that represent molecular relationships between proteins/genes associated with BA and TB, thus facilitating a better understanding of the biological context of antagonistic relationships between the diseases. The results of our study revealed a number of proteins/genes important for the development of both BA and TB.