Premium
HLA Dr‐Dq haplotypes and the TNFA‐308 polymorphism: associations with asthma and allergy
Author(s) -
MuntheKaas M. C.,
Carlsen K. L.,
Carlsen K. H.,
Egeland T.,
Håland G.,
Devulapalli C. S.,
Akselsen H.,
Undlien D.
Publication year - 2007
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/j.1398-9995.2007.01377.x
Subject(s) - immunology , linkage disequilibrium , allergy , haplotype , asthma , allele , human leukocyte antigen , medicine , genetics , biology , gene , antigen
Background: The HLA (human leukocyte antigen) class II genes DQB1 and DRB1 and the Tumor Necrosis Factor α gene ( TNFA ) within the HLA complex (chromosome 6p21) have been associated with asthma and allergy. Due to the strong linkage disequilibrium characterizing this complex and the multiple asthma/allergy expressions, we aimed to determine which of these genes were primarily involved in specific asthma/allergy traits. Methods: The DRB1 – DQB1 alleles and TNFA ‐308 polymorphism were genotyped in 959 children from the Environment and Childhood Asthma study and analyzed for possible associations with allergic and non‐allergic asthma (with/without at least one positive skin prick test for allergens) and specific allergic sensitization, as well as bronchial hyperresponsiveness and total IgE, using both allele and extended haplotype analyses. Results: Different genes within the HLA complex were associated with separate asthma and allergy traits. Nonallergic asthma was associated with both the TNFA ‐308A allele [Odds ratio (OR) 1.7 (1.3–2.3)] and DRB1* 03 allele [OR 1.6(1–2.6)], but extended DRB1 *03‐ TNFA ‐308 haplotype analysis suggested that the DRB1 – DQB1 association was secondary to linkage disequilibrium with the TNFA ‐308 polymorphism. Allergies were associated with HLA class II alleles only; birch sensitization with DQB1 *0603‐ DRB1 *13 [OR 2.3 (1.4–4.0)] and mugwort sensitization with DQB1 *0609‐ DRB1 *13 [OR 7.1 (1.9–27.0)] and DQB1 *0501‐ DRB1 *01 [OR 2.0 (1.0–4.0)]. Conclusions: Our data suggests that asthma is not associated with DRB1 or DQB1 but rather TNFA or a gene(s) in linkage disequilibrium, while sensitization to specific allergens is associated with particular alleles at the DQ and/or DR loci. A novel association between DQB1 *0603‐ DRB1 *13 and birch allergy is identified.