NEW YORK (Reuters Health) - Spirometric values and bronchodilator responsiveness in patients with asthma appear to be linked to different single nucleotide polymorphisms (SNPs) in the beta-2-adrenergic receptor (B2AR) gene, investigators in Boston report.
B2AR, located on lymphocytes and airway smooth muscle cells, is often downregulated in asthmatic patients. Although case-control studies have shown that B2AR polymorphisms are associated with numerous asthma-related phenotypes, evidence pertaining to specific polymorphisms have been inconsistent.
Therefore, Dr. Edwin K. Silverman, at Brigham and Women’s Hospital, and associates conducted a family-associated association analysis, which included 707 “exceptionally well-phenotyped patients” with mild to moderate asthma enrolled in the Childhood Asthma Management program and their parents. Blood samples were analyzed for eight individual single nucleotide polymorphisms (SNPs).
According to their report in the Journal of Allergy and Clinical Immunology for November, the +523 SNP was associated with bronchodilator responsiveness. The authors believe that this SNP is probably not the key functional variant; instead, it may be in linkage disequilibrium with an untyped functional variant within or beyond the B2AR gene.
There were 20 subjects with FEV1 < 80% predicted, among whom there was significant association with SNPs -654, -47, +46 and +79 (p = 0.002 or less). Among 13 subjects with FVC < 80% predicted, there was an association for the -654 (p = 0.02) and +46 (p = 0.007) SNPs. The authors caution that the small number of affected patients lends uncertainly to the validity of these associations.
Quantitative analysis revealed significant associations with percent predicted FEV1 and SNP -654 and SNP +46.
Dr. Silverman’s team found no evidence of an association between B2AR variants and asthma severity, allergy skin test results, or peak expiratory flow rate. Among the 516 white subjects only, they observed genotype effects on IgE levels and methacholine challenge testing.
“Future investigation of additional genetic variants near the B2AR gene... might clarify the functional asthma genetic determinants within this region,” the investigators conclude.
Source: J Allergy Clin Immunol 2003;112:870-876. [ Google search on this article ]
MeSH Headings:Membrane Proteins: Receptors, Adrenergic: Receptors, Adrenergic, beta: Receptors, Cell Surface: Receptors, Neurotransmitter: Receptors, Biogenic Amine: Receptors, Catecholamine: Polymorphism, Single NucleotideCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
