Air pollution and allergic diseases.

PURPOSE OF REVIEW: Exposure to traffic-related air pollutants (TRAPs) has been implicated in asthma development, persistence, and exacerbation. This exposure is highly significant because increasingly large segments of the population worldwide reside in zones that have high levels of TRAP, including children, as schools are often located in high traffic pollution exposure areas. RECENT FINDINGS: Recent findings include epidemiologic and mechanistic studies that shed new light on the impact of traffic pollution on allergic diseases and the biology underlying this impact. In addition, new innovative methods to assess and quantify traffic pollution have been developed to assess exposure and identify vulnerable populations and individuals. SUMMARY: This review will summarize the most recent findings in each of these areas. These findings will have a substantial impact on clinical practice and research by the development of novel methods to quantify exposure and identify at-risk individuals, as well as mechanistic studies that identify new targets for intervention for individuals most adversely affected by TRAP exposure.

Identification of KIF3A as a novel candidate gene for childhood asthma using RNA expression and population allelic frequencies differences.

BACKGROUND: Asthma is a chronic inflammatory disease with a strong genetic predisposition. A major challenge for candidate gene association studies in asthma is the selection of biologically relevant genes. METHODOLOGY/PRINCIPAL FINDINGS: Using epithelial RNA expression arrays, HapMap allele frequency variation, and the literature, we identified six possible candidate susceptibility genes for childhood asthma including ADCY2, DNAH5, KIF3A, PDE4B, PLAU, SPRR2B. To evaluate these genes, we compared the genotypes of 194 predominantly tagging SNPs in 790 asthmatic, allergic and non-allergic children. We found that SNPs in all six genes were nominally associated with asthma (p<0.05) in our discovery cohort and in three independent cohorts at either the SNP or gene level (p<0.05). Further, we determined that our selection approach was superior to random selection of genes either differentially expressed in asthmatics compared to controls (p = 0.0049) or selected based on the literature alone (p = 0.0049), substantiating the validity of our gene selection approach. Importantly, we observed that 7 of 9 SNPs in the KIF3A gene more than doubled the odds of asthma (OR = 2.3, p<0.0001) and increased the odds of allergic disease (OR = 1.8, p<0.008). Our data indicate that KIF3A rs7737031 (T-allele) has an asthma population attributable risk of 18.5%. The association between KIF3A rs7737031 and asthma was validated in 3 independent populations, further substantiating the validity of our gene selection approach. CONCLUSIONS/SIGNIFICANCE: Our study demonstrates that KIF3A, a member of the kinesin superfamily of microtubule associated motors that are important in the transport of protein complexes within cilia, is a novel candidate gene for childhood asthma. Polymorphisms in KIF3A may in part be responsible for poor mucus and/or allergen clearance from the airways. Furthermore, our study provides a promising framework for the identification and evaluation of novel candidate susceptibility genes.

Genetic biomarkers of health-related quality of life in pediatric asthma.

OBJECTIVES: To determine the relationship between single nucleotide polymorphisms in candidate genes associated with multiple asthma phenotypes and health-related quality of life (HRQOL). STUDY DESIGN: A cross-sectional study was conducted at a pediatric hospital in 275 school-aged children diagnosed with asthma and their caregivers. Genomic DNA was obtained from children, and caregivers completed a measure of their child's HRQOL. Analysis of variance was used to investigate the association between single nucleotide polymorphisms and HRQOL. RESULTS: Children homozygous for the major variant at IL-4RA rs 1805010 had significantly better HRQOL than their counterparts. Significant associations with pulmonary function were not observed. CONCLUSIONS: Genes associated with asthma phenotype can be associated with HRQOL at least partly independent of pulmonary function.