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Beta2-adrenergic receptor haplotype/polymorphisms and asthma susceptibility and clinical phenotype in a Chinese Han population

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Abstract:

Association and linkage studies of beta2-adrenergic receptor (beta2AR) polymorphisms in relation to the expression of asthmatic phenotypes and immune regulatory mechanisms have shown inconsistent results. This study was designed to analyze the relationship of particular combinations of single nucleotide polymorphisms (SNPs) or haplotypes of the beta2AR gene with bronchial asthma, bronchodilator response, and total IgE. By direct DNA sequencing, five SNPs (in positions −47, −20, 46, 79, and 252) of beta2AR gene were determined and combined with haplotypes in 201 asthmatic patients and 276 normal controls recruited from the Chinese Han population. Significantly higher bronchodilator response was observed in patients with homozygotic genotype 46A/A (13.40 ± 3.48%), compared with those with homo-46G/G (7.25 ± 3.11%) and heterozygotes 46A/G (7.39 ± 3.14%), respectively (p < 0.0001). There was also a significant difference in bronchodilator response when beta2AR haplotypes were analyzed (p = 0.003). From two common SNPs at positions 46A/G and 79C/G, we had determined three haplotypes that constructed six haplotype pairs. Comparison of the mean delta forced expiratory volume in 1 second (FEV1) values for the six haplotype pairs showed significant difference. Subjects homozygous for 46A/79C (Arg16/Gln27) had the highest deltaFEV1 (13.40 ± 3.48%) and those with 46G/79C (Gly16/Gln27) homozygote had the lowest (6.43 ± 0.55%). The two SNP haplotype pairs were significantly associated with delta FEV1 (p < 0.0001). Significantly higher total IgE levels were found in patients with homozygotic carriers of 79C genotypes (p = 0.022) and homozygotic haplotype −47 T/−20 T/46 A/79 C/252 G (p < 0.0001). These results indicate that the manifestation of asthma might be affected by either an individual beta2AR SNPs or beta2AR haplotype.

Document Type: Research Article

DOI: http://dx.doi.org/10.2500/aap.2010.31.3371

Affiliations: Department of Respiratory Medicine, Drum Tower (Gulou) Hospital Affiliated with Nanjing University Medical School, Nanjing, China

Publication date: September 1, 2010

More about this publication?
  • Allergy and Asthma Proceedings is a peer reviewed publication dedicated to distributing timely scientific research regarding advancements in the knowledge and practice of allergy, asthma and immunology. Its primary readership consists of allergists and pulmonologists.

    The goal of the Proceedings is to publish articles with a predominantly clinical focus which directly impact quality of care for patients with allergic disease and asthma.

    Featured topics include asthma, rhinitis, sinusitis, food allergies, allergic skin diseases, diagnostic techniques, allergens, and treatment modalities. Published material includes peer-reviewed original research, clinical trials and review articles.

    Articles marked "F" offer free full text for personal noncommercial use only.

    The journal is indexed in Thomson Reuters Web of Science and Science Citation Index Expanded, plus the National Library of Medicine's PubMed service.
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