Assuntos
Arachis/imunologia , Asma/genética , Asma/imunologia , Antígenos HLA/genética , Hipersensibilidade a Amendoim/genética , Hipersensibilidade a Amendoim/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Canadá , Criança , Pré-Escolar , Feminino , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Peanut allergy (PA) is a complex disease with both environmental and genetic risk factors. Previously, PA loci were identified in filaggrin (FLG) and HLA in candidate gene studies, and loci in HLA were identified in a genome-wide association study and meta-analysis. OBJECTIVE: We sought to investigate genetic susceptibility to PA. METHODS: Eight hundred fifty cases and 926 hyper-control subjects and more than 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. A meta-analysis of 2 phenotypes (PA and food allergy) was conducted by using 7 studies from the Canadian, American (nâ¯=â¯2), Australian, German, and Dutch (nâ¯=â¯2) populations. RESULTS: An SNP near integrin α6 (ITGA6) reached genome-wide significance with PA (Pâ¯=â¯1.80â¯×â¯10-8), whereas SNPs associated with Src kinase-associated phosphoprotein 1 (SKAP1), matrix metallopeptidase 12 (MMP12)/MMP13, catenin α3 (CTNNA3), rho GTPase-activating protein 24 (ARHGAP24), angiopoietin 4 (ANGPT4), chromosome 11 open reading frame (C11orf30/EMSY), and exocyst complex component 4 (EXOC4) reached a threshold suggestive of association (Pâ¯≤â¯1.49â¯×â¯10-6). In the meta-analysis of PA, loci in or near ITGA6, ANGPT4, MMP12/MMP13, C11orf30, and EXOC4 were significant (Pâ¯≤â¯1.49â¯×â¯10-6). When a phenotype of any food allergy was used for meta-analysis, the C11orf30 locus reached genome-wide significance (Pâ¯=â¯7.50â¯×â¯10-11), whereas SNPs associated with ITGA6, ANGPT4, MMP12/MMP13, and EXOC4 and additional C11orf30 SNPs were suggestive (Pâ¯≤â¯1.49â¯×â¯10-6). Functional annotation indicated that SKAP1 regulates expression of CBX1, which colocalizes 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 PA and food allergy. Multiple genes (C11orf30/EMSY, SKAP1, and CTNNA3) identified by this study are involved in epigenetic regulation of gene expression.
Assuntos
Epigênese Genética , Loci Gênicos , Estudo de Associação Genômica Ampla , Proteínas de Neoplasias/genética , Proteínas Nucleares/genética , Hipersensibilidade a Amendoim/genética , Polimorfismo de Nucleotídeo Único , Proteínas Repressoras/genética , Homólogo 5 da Proteína Cromobox , Feminino , Proteínas Filagrinas , Humanos , Masculino , Hipersensibilidade a Amendoim/epidemiologia , Hipersensibilidade a Amendoim/metabolismo , Fosfoproteínas/biossíntese , Fosfoproteínas/genética , Fatores de Risco , alfa Catenina/biossíntese , alfa Catenina/genéticaAssuntos
Fatores Etários , Anafilaxia/epidemiologia , Hipersensibilidade Alimentar/epidemiologia , Alérgenos/imunologia , Canadá/epidemiologia , Criança , Pré-Escolar , Exposição Ambiental , Epinefrina/administração & dosagem , Feminino , Humanos , Imunoglobulina E/metabolismo , Incidência , Lactente , Masculino , Fatores de Risco , Sesamum/imunologiaRESUMO
BACKGROUND: We previously estimated that the annual rate of accidental exposure to peanut in 1411 children with peanut allergy, followed for 2227 patient-years, was 11.9% (95% CI, 10.6, 13.5). This cohort has increased to 1941 children, contributing 4589 patient-years, and we determined the annual incidence of accidental exposure, described the severity, management, location, and identified associated factors. FINDINGS: Children with physician-confirmed peanut allergy were recruited from Canadian allergy clinics and allergy advocacy organizations from 2004 to May 2014. Parents completed questionnaires regarding accidental exposure to peanut over the preceding year. Five hundred and sixty-seven accidental exposures occurred in 429 children over 4589 patient-years, yielding an annual incidence rate of 12.4% (95% CI, 11.4, 13.4). Of 377 accidental exposures that were moderate or severe, only 109 (28.9%) sought medical attention and of these 109, only 40 (36.7%) received epinephrine. Of the 181 moderate/severe accidental exposures treated outside a health care facility, only 11.6% received epinephrine. Thirty-seven percent of accidental exposures occurred at home. In multivariate analyses, longer disease duration, recruitment through an allergy advocacy association, and having other food allergies decreased the likelihood of accidental exposures. Age ≥ 13 years at study entry and living with a single parent increased the risk. CONCLUSION: Despite increased awareness, accidental exposures continue to occur, mainly at home, and most are managed inappropriately by both health care professionals and caregivers. Consequently, more education is required on the importance of strict allergen avoidance and the need for prompt and correct management of anaphylaxis.
