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 reduction measures in houses of allergic asthmatic patients:Effects of air-cleaners and allergen-impermeable mattress covers

Recommendations for allergen avoidance or allergen reduction measures play an important part in the treatment of allergic asthmatic patients. The purpose of this study was to test recently developed air-cleaners with respect to their capacity to capture airborne allergen particles and to improve clinical parameters of asthmatic patients sensitized to aeroallergens. Forty five allergic asthmatic patients were studied in a double-blind procedure for 6 months, The patients were divided into three groups of 15 patients. In Group 1, the intervention consisted of the application of active air-cleaners in living-rooms and bedrooms, In Group 2, placebo air-cleaners were used in combination with allergen-impermeable mattress covers, In Group 3, the same intervention was performed as in Group 2 but with active air-cleaners. Allergen levels in mattress and floor dust were measured before, and 3 and 6 months after the interventions, After 6 months, the air-cleaners were dismantled and the filters were analysed for the amount of dust collected and allergen content, Immunological and lung function parameters were measured before, and 3 and 6 months after the interventions. Considerable amounts of airborne dust and allergenic particles were captured in the filters of the air-cleaners, Up to the 18.9 g of dust, 4,513 ng of house dust mite allergen, Der p 1, and 50,000 mU of cat allergen, Fel d 1, (in houses with cats) were collected by air-cleaners in living-rooms, Only in Group 3 (in which both active air-cleaners and mattress covers were used) was a small (less than 1 doubling dose) but statistically significant improvement of provocative concentration of histamine causing a 20% fall in forced expiratory volume in one second (PC20) observed (from 5.96 to 9.02 mg mL(-1)). The amount of dust and house dust mite allergen collected in the filters was significantly correlated with an improvement of peak flow variation. In combination with other allergen avoidance measures, the examined air-cleaners can contribute to diminished allergen exposure and improvement of airway hyperresponsiveness in asthmatic patients

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