Chest

Chest

Volume 130, Issue 2, August 2006, Pages 449-454
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Original Research: ASTHMA
Association Between Nonspecific Airway Hyperresponsiveness and Arg16Gly β2-Adrenergic Receptor Gene Polymorphism in Asymptomatic Healthy Japanese Subjects

https://doi.org/10.1378/chest.130.2.449Get rights and content

Background

Nonspecific airway hyperresponsiveness (AHR), a cardinal feature of asthma, is thought to result from several genetic and environmental factors. Asymptomatic AHR in nonasthmatic healthy subjects might be a risk factor for the development of asthma. Genetic variations in codons 16 and 27 of the human β2-adrenergic receptor (β2-AR) alter receptor function in vitro and are associated with various asthma-related phenotypes, including asthma severity and AHR. To date, however, few reports have examined the impact of β2-AR gene polymorphism on AHR in asymptomatic healthy subjects.

Objective

To determine whether polymorphism of the β2-AR gene (Arg16Gly and Gln27Glu) might influence nonspecific AHR in asymptomatic healthy Japanese subjects.

Design and participants

A cohort of 120 asymptomatic healthy subjects was analyzed using a stepwise linear regression model. Nonspecific airway responsiveness was measured using a continuous methacholine inhalation method (Astograph; Chest; Tokyo, Japan). We used values of the cumulative dose of inhaled methacholine measured at the inflection point at which respiratory conductance starts to decrease (Dmin) as an index of AHR. Genotyping to identify polymorphisms at codons 16 and 27 was conducted using an assay combining kinetic real-time quantitative polymerase chain reaction with allele-specific amplification.

Results

The Gly16Gly genotype was associated with lower Dmin values. The log Dmin value of asymptomatic healthy subjects carrying the Arg16 allele (Arg16/Arg or Arg16/Gly, n = 90) was 1.09 ± 0.56 (mean ± SD), while those homozygous for the Gly16 allele (n = 30) yielded a log Dmin value of 0.85 ± 0.56 (p < 0.05).

Conclusion

This study indicates that a specific β2-AR polymorphism at codon 16 might be a genetic determinant of AHR, as judged by methacholine-induced bronchoconstriction in asymptomatic healthy subjects.

Section snippets

Study Subjects

One hundred twenty asymptomatic healthy subjects (87 men and 33 women; median age, 24 years; range, 18 to 35 years) were recruited for this study (Table 1). The subjects were medical students from Hokkaido University and were living in Sapporo, Japan. All subjects gave written informed consent for enrollment in this study and all associated procedures. All participants underwent structured interviews and completed questionnaires regarding history of allergic or respiratory disease, as well as

RESULTS

In this study, 74.2% of subjects (n = 89) had specific IgE antibodies to at least 1 of 14 inhaled antigens, including D farinae, grass pollens, animal dander, and molds (Table 1). Seventy-seven subjects (64.2%) had specific IgE to D farinae. Twenty-nine subjects (24.2%) had allergic rhinitis. Thirteen subjects (10.8%) had a family history of asthma. Fifty-seven of 91 subjects (62.6%) had concentrations of mite antigens (Der p 1 and Der f 1) > 2 μg/g of dust in their bedding, which is reportedly

DISCUSSION

Several studies have examined possible relationships between β2-AR polymorphisms and AHR, a cardinal feature of asthma. Although some of the results are conflicting, it is clear that the β2-AR gene determines the degree of airway responsiveness in a number of different populations.111718282930 In the present study, we investigated whether polymorphism at codon 16 might influence airway responsiveness among asymptomatic healthy individuals, and found an association between presence of the Arg16

ACKNOWLEDGMENT

We thank all the subjects of this study for their participation. We also thank Yoshiko Obata and Kotomi Hosono for technical assistance. We also thank Ken Sawazaki at the Pharmaceutical Research Laboratory, Hitachi Chemical Co., Ltd., for measuring specific IgE antibody levels (multiple radioallergosorbent test).

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    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestjournal.org/misc/reprints.shtml)

    This study was funded in part by Grant-in-Aid for Scientific Research 13670585 from the Japan Society for the Promotion of Science.

    No author has any conflict of interest with respect to this article.

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