Genetics, atopy asthma

Asthma is a complex disease which is due to the interaction of an unknown number of genes with strong environmental factors. Segregation analysis suggests the presence of major genes underlying asthma and atopy. Different genetic effects have been recognized which predispose to generalized atopy, or modify the atopic response to particular allergens, or enhance bronchial inflammation, or modify bronchial tone. These known genes or genetic loci do not account for all of the familial clustering of asthma and atopy. Many studies are now under way to identify the remaining genes

The Impact of Persistent Bacterial Bronchitis on the Pulmonary Microbiome of Children

Persistent bacterial bronchitis (PBB) is a leading cause of chronic cough in young children and yet the condition is poorly understood. Current management involves prolonged antibiotic treatment, however, early diagnosis is key to improving patient outcomes. <div>This study investigated the differences in the bacterial community in the lower respiratory tract of healthy children compared to those with PBB, using both blind and non-blind lung brushings. The less invasive blind brushing method was shown to provide robust data regarding the lower airways microbiome in this condition and thus provides an opportunity to further our understanding of the dynamics of the lower airways microbiome in health and disease.</div

Meta-analysis for linkage to asthma and atopy in the chromosome 5q31-33 candidate region.

Asthma is a common, complex human disease. Gene discovery in asthma has been complicated by substantial etiological heterogeneity, the possibility of genes of small effect and the concomitant requirement for large sample sizes. Linkage to asthma phenotypes has been investigated most intensively in the 5q chromosomal region, although results have been inconsistent across studies and all studies have had modest sample sizes. One potential solution to these issues is to combine data from multiple studies in a retrospective meta-analysis by pooling either summary statistics or raw data. The International Consortium on Asthma Genetics combined data from 11 data sets (n = 6277 subjects) to investigate evidence for linkage of 35 markers spanning the cytokine cluster on chromosome 5q31–33 to 'asthma' dichotomy and total serum immunoglobulin E (IgE) levels. Chromosome 5q markers typed in different centers were integrated into a consensus map to facilitate effective data pooling. Multipoint linkage analyses using a new Haseman–Elston method were performed with all data sets pooled together, and also separately with the resulting linkage statistics pooled by meta-analytic methods. Our results did not provide any evidence significant at the 5% level that loci conferring susceptibility to asthma or atopy are present in the 5q31–33 region; however, there was some weak evidence (empirical P = 0.077) of linkage to asthma affection. This study suggests that loci in 5q31–33 have at most a modest effect on susceptibility to asthma or total serum IgE levels, may not be detectable or present in all human populations and are difficult to detect even using combined linkage evidence from 2400–2600 full sibling pairs

Gene polymorphism in Netherton and common atopic disease.

Atopic dermatitis (AD) and asthma are characterized by IgE-mediated atopic (allergic) responses to common proteins (allergens), many of which are proteinases. Loci influencing atopy have been localized to a number of chromosomal regions, including the chromosome 5q31 cytokine cluster. Netherton disease is a rare recessive skin disorder in which atopy is a universal accompaniment. The gene underlying Netherton disease (SPINK5) encodes a 15-domain serine proteinase inhibitor (LEKTI) which is expressed in epithelial and mucosal surfaces and in the thymus. We have identified six coding polymorphisms in SPINK5 (Table 1) and found that a Glu420--&gt;Lys variant shows significant association with atopy and AD in two independent panels of families. Our results implicate a previously unrecognized pathway for the development of common allergic illnesses