Genetic determinants in the development of sensitization to environmental allergens in early childhood

Immunity, Inflammation and Disease

Priya Tripathi²  Xiumei Hong¹  Deanna Caruso¹  Peisong Gao² 

[1] Center on Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland;Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, Maryland

关键词: Asthma;    allergic sensitization;    cockroach sensitization;    house dust mites;    single nucleotide polymorphisms;   

DOI  :  10.1002/iid3.38

来源: Wiley

【 摘 要 】

Abstract

Sensitization to environmental allergens remains one of the strongest risk factors for asthma, and there is likely a genetic basis. We sought to identify genetic determinants for the development of allergic sensitization to environmental allergens, particularly cockroach allergen, in early childhood. A total of 631 children with the information about genotypic data on 895 single nucleotide polymorphisms (SNPs) in 179 candidate genes were selected from an existing dataset (Boston Birth Cohort). Genetic analysis was performed for allergic sensitizations among all subjects and sub-population, Black/African, respectively. Eight SNPs in seven genes showed significant association with allergic sensitization with P < 0.05, including two top SNPs, rs7851969 in JAK2 (P = 0.003) and rs11739089 in CNOT6 (P = 0.008). When analyses were specifically performed for cockroach sensitization, 16 SNPs in 13 genes showed P < 0.05, including five genes with SNPs at P < 0.01 (JAK1, JAK3, IL5RA, FCER1A, and ADAM33). Particularly, haplotype analyses demonstrated that multiple-haplotypes in FCER1A were significantly associated with cockroach sensitization with the strongest association for a 2-marker haplotype (rs6665683T-rs12136904T, P = 0.001). Furthermore, SNP rs6665683 was marginally associated with the levels of cockroach allergen specific IgE. When a similar analysis was performed for house dust mite, four SNPs in three genes (JAK2, MAML1, and NOD1) had P < 0.01. Of these, JAK2 appeared to be an only gene showing association across the sensitizations we analyzed. Some of findings were further validated when analysis was limited to black population. Our study identified several loci that may confer the susceptibility to allergic sensitization, and suggested that sensitization to allergens may depend on their unique loci.

【 授权许可】

CC BY   
© 2014 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.