β2-ADR haplotypes/polymorphisms associate with bronchodilator response and total IgE in grass allergy

Abstract

Association and linkage studies of β2-adrenergic receptor (β2-ADR) polymorphisms in relation to the expression of asthmatic phenotypes and immune regulatory mechanisms have shown inconsistent results. In order to analyse the relevance of particular combinations of single nucleotide polymorphisms (SNPs) or haplotypes of β2-ADR gene to bronchial asthma, bronchodilator response and total immunoglobulin E (IgE) we determined by direct DNA sequencing five SNPs (in positions: -47, -20, 46, 79, 252) in a group of 180 Caucasian subjects (110 patients with grass allergy and 70 nonatopic controls). The eight different β2-ADR haplotypes were identified, with three the most common of them representing 92% of the studied cohort. Significantly higher (pcor = 0.0045) bronchodilator response was observed in patients with homozygotic genotype 46A/A in comparison with respective homo- and hetero-zygotes. There was no significant difference in bronchodilator response when β2-ADR haplotypes were analysed. Significantly higher (pcor = 0.0005) total IgE levels were found in patients with β2-ADR haplotype -47T/-20T/46A/79C/252G and homozygotic carriers of 46A (pcor = 0.0015) and 79C (pcor = 0.003) genotypes. No significant associations were found in regards to asthmatic phenotype and atopy. These results indicate that depending on phenotype studied, either an individual β2-ADR SNP or β2-ADR haplotype might affect disease manifestation. Copyright © Blackwell Munksgaard 2005.