Genome-wide association study and meta-analysis in multiple populations identifies new loci for peanut allergy and establishes C11orf30/EMSY as a genetic risk factor for food allergy

BACKGROUND: Peanut allergy (PA) is a complex disease with both environmental and genetic risk factors. Previously PA loci were identified in FLG and HLA in candidate gene studies, and loci in HLA in a genome-wide association study and meta-analysis. OBJECTIVE: To investigate genetic susceptibility to PA. METHODS: Eight hundred and fifty cases and 926 hyper-controls and >7.8 million genotyped and imputed single nucleotide polymorphisms (SNPs) were analyzed in a genome-wide association study to identify susceptibility variants for PA in the Canadian population. Meta-analysis of two phenotypes (PA and food allergy) was conducted using 7 studies from the Canadian, American (2), Australian, German and Dutch (2) populations. RESULTS: A SNP near ITGA6 reached genome-wide significance with PA (p=1.80×10(-8)), while SNPs associated with SKAP1, MMP12/MMP13, CTNNA3, ARHGAP24, ANGPT4, c11orf30 (EMSY), and EXOC4 reached a threshold suggestive of association (p≤1.49×10(-6)). In the meta-analysis of PA, loci in or near ITGA6, ANGPT4, MMP12/MMP13, c11orf30 and EXOC4 were significant (p≤1.49×10(-6)). When a phenotype of any food allergy was used for meta-analysis, the c11orf30 locus reached genome-wide significance (p=7.50×10(-11)), while SNPs associated with ITGA6, ANGPT4, MMP12/MMP13, EXOC4 and additional c11orf30 SNPs were suggestive (p≤1.49×10(-6)). Functional annotation indicated SKAP1 regulates expression of CBX1, which co-localizes with the EMSY protein coded by c11orf30. CONCLUSION: This study identifies multiple novel loci as risk factors for PA and food allergy and establishes c11orf30 as a risk locus for both peanut and food allergy. Multiple genes (c11orf30/EMSY, SKAP1 and CTNNA3) identified by this study are involved in epigenetic regulation of gene expression

Allergen-avoidance measures in homes of house-dust-mite-allergic asthmatic patients:effects of acaricides and mattress encasings

This double-blind, placebo-controlled study investigated whether the application of an acaricide (Acarosan(R)) on mattresses and on textile floor coverings in living rooms and bedrooms can contribute to improvement in lung function and airway hyperresponsiveness in 40 adult asthmatic patients sensitized to house-dust mite. In a second group of 19 patients who refused chemical intervention, the clinical effects of application of allergen-impermeable mattress encasings were studied. In all three treatment groups, Der p 1 levels in mattress dust were statistically significantly decreased after 12 months. However, this decrease was much greater in the group who received mattress encasings (final mean level 430 ng/g) than in groups with acaricide-or placebo-treated mattresses (final mean levels 1730 and 2100 ng/g, respectively). Treatment of textile floors with either Acarosan or placebo chemical caused a statistically significant decrease in the level of the house-dust-mite allergen Der p 1 in floor dust. In the group with mattress encasings, no significant changes of floor dust Der p 1 were found. Airway hyperresponsiveness (as measured by the PC20, histamine) improved significantly in the mattress cover group after 6 months. The Acarosan group also showed a small but statistically significant improvement after 12 months

OCCUPATIONAL ASTHMA IN ALUMINUM POTROOM WORKERS RELATED TO PREEMPLOYMENT EOSINOPHIL COUNT

Occupational asthma still occurs in aluminium potroom workers despite pre-employment medical selection, The purpose of our study was to identify workers with an increased risk of developing ''potroom asthma''. A nested, case-control study was carried out in two Dutch aluminium producing plants, Pre-employment data of 364 potroom workers (182 cases and 182 controls) were analyzed, Cases were workers unable to work because of work-related respiratory disease, meeting the criteria for potroom asthma The selected controls were matched for age, year of starting employment and working conditions. Pre-employment eosinophil count was significantly related to the occurrence of potroom asthma, even though the mean number of the eosinophils in cases was within the normal range (220cells . mm(-3); 0.22 cellsx10(9) . L(-1)) developed potroom asthma with time. We conclude that workers without respiratory symptoms, with normal lung function and normal bronchial responsiveness before employment developed potroom asthma Fluoride exposure, combined with an elevated eosinophil count, might induce an immunological or cytotoxic process

Ross Volunteers - 63

Corps of Cadets: Ross Volunteer