Discovery of genetic difference between asthmatic children with high IgE level and normal IgE level by whole genome linkage disequilibrium mapping using 763 autosomal STR markers

Abstract

The genome-wide linkage disequilibrium screen for loci associated with genetic difference between allergic and nonallergic asthma was conducted with 763 autosomal STR markers and included 190 asthmatic children. Evidence for association with differences between the two forms of asthma was observed for 36 STR markers. Marker-to-marker synergetic effect and by simulation resampling tests revealed D5S2011, D6S305, and D9S286 were important loci in allergic asthma while D6S1574, D8S1769, and D19S226 were important in nonallergic asthma. Our results show strong genetic evidence that these markers play an important role in defining allergic and nonallergic asthma and provides important candidates of susceptible genes in these two categories of asthma. This study further shows that asthma is, indeed, a heterogeneous group of underlying diseases and, although with similar clinical phenotypes, may have different clinical severities, outcomes, and need more tailor-made management.

Association of CD14 promoter polymorphisms and soluble CD14 levels in mite allergen sensitization of children in Taiwan

“…The results of association studies of the CD14 gene with allergic asthma in our populations further emphasize the importance of environmental exposure in the development of allergen sensitization in children. Previously, we have found that D5S2011 (near CD14 genes) differs highly significantly between allergy and nonallergic asthma (Wang et al 2005b). In this study, we have shown that the increase in soluble CD14 levels is inversely correlated with total serum IgE concentrations in our study population.…”

The polymorphisms of protein-tyrosine phosphatase receptor-type delta gene and its association with pediatric asthma in the Taiwanese population

“…The definition of asthma must meet the following criteria: (1) a history of having wheezing and experiencing shortness of breath during or without concurrent respiratory infections, (2) chronic coughing for more than 1 month and being diagnosed by a physician for the presence of wheezing episode(s) and (3) positive bronchodilator test showing a 15% increase in FEV1. Nonasthma controls were defined as those without an asthma history as in criteria (1) or those who did not meet criteria (2). Other evaluations included skin prick tests for responsiveness to six common aeroallergens, a differential blood count (including total eosinophil count) and levels of total serum IgE, as well as IgE specific to house dust and mixed pollens, using the Unicap system (Pharmacia Diagnostic, Sweden).…”

“…D9S286, one of the six STR loci, was located on chromosome 9p arm and its physical distance from p terminus is 8.04 Mb. 1 Protein-tyrosine phosphatase receptor-type delta (PTPRD) gene is the closest gene to the D9S286 locus with a physical distance of 8. 3 -8.72 Mb from chromosome 9p terminus (ref.…”

Variant in Promoter Region of Platelet-Derived Growth Factor Receptor-α (PDGFRα) Gene Is Associated with the Severity and Allergic Status of Childhood Asthma

“…In our previous study comparing the genetic profiling of allergic and nonallergic asthmatic children, we found that asthmatic children with atopic status and high serum IgE (>1,000 IU) levels were more prone to develop more severe and persistent asthma than nonallergic asthma [10]. Whether this status is related to the progression of airway remodeling is not known.…”

“…It was suggested that the upregulation of PDGFRα by FGF-β, IL-1β and TGF-β contributes to cellular hyperplasia of bronchial smooth muscles during chronic airway inflammation in asthma [9]. Using short tandem repeats (STR) markers in whole genome linkage disequilibrium mapping, we found that allele frequencies of several STR markers were significantly associated with childhood asthma [10], in which the PDGFRA gene is located at chromosome 4q12 between two statistically significant STR markers, D4S2971 and D4S1592, found in earlier reports by us [10, 11]. …”