HLA-DQB1*02 and DQB1*06:03P are associated with peanut allergy

Abstract

Peanut allergy (PA) is a common and serious food allergy and its prevalence has increased in the past decade. Although there is strong evidence of inheritance, the genetic causes of this disease are not well understood. Previously, a large-scale genome-wide association study described an association between human leukocyte antigen (HLA)-DQB1 and asthma; the aim of this study was to evaluate the association between HLA-DQB1 and PA. Genotypic and allelic profiles were established for 311 Caucasian members of a well-described Canadian group of children with PA and 226 Caucasian controls. Firth's logistic regression analyses showed associations between HLA-DQB1 alleles and PA for DQB1*02 (P=1.1 × 10(-8), odds ratio (OR)=0.09 (CI=0.03-0.23)) and DQB1*06:03P alleles (P=2.1 × 10(-2), OR=2.82 (CI=1.48-5.45)). This study of HLA in PA demonstrates specific association between two allelic groups of the HLA-DQB1 gene (DQB1*02 and DQB1*06:03P) and PA, highlighting its possible role in the development of this disease.

Figure 1

Distribution of each HLA-DQB1 genotype for peanut allergic subjects and controls. Bar graphs represent the genotypic frequencies in percentages for peanut allergic subjects and controls for each studied allele of the HLA-DQB1 loci. Numbers of subjects for each genotype are also indicated. Results for HLA-DQB1*02 are shown in figure a, for HLA-DQB1*03 in b, for HLA-DQB1*03:01P in c, for HLA-DQB1*03:02P in d, for HLA-DQB1*03:03P in e, for HLA-DQB1*04 in f, for HLA-DQB1*05 in g, for HLA-DQB1*05:01P in h, for HLA-DQB1*06 in i, for HLA-DQB1*06:02P in j, for HLA-DQB1*06:03P in k, and for HLA-DQB1*06:14P in l. For example, Figure 1a shows a frequency of 4.0% among controls (representing 9 carriers) for the DQB1*02 homozygotes (DQB1*02+DBQ1*02) and a frequency of 2.6% (for 8 carriers) among PA cases, a frequency of 28.3% (for 64 carriers) of heterozygotes among controls for the DQB1*02 allele (DQB1*02+DQB1* any other allele) and 2.9% (for 9 carriers) among PA cases and finally a frequency of 67.7% (for 153 carriers) among controls for all other subjects that do not carry any DQB1*02 alleles and 94.5% (for 294 carriers) among PA cases. Alleles and genotypes as indicated in the ImMunoGeneTics (IMGT)/HLA database nomenclature version 3.5.0 (July 2011). Alleles with two sets of two digits and a ‘P' are P groups of alleles comprising HLA-DQB1 alleles that share the same PBD. Alleles with only one set of two digits are those that include a mix of rare alleles because of their low frequency in the studied population (see Supplementary Table S4 in the Supplementary Materials for a list of those alleles). Het, heterozygotes for the studied allele; Homo, homozygotes for the studied allele; NC, non-carrier of this allele.