1999 Fiscal Year Final Research Report Summary
Molecular Pathophysiology of Asthma: Relationship between β2-adrenergic receptor gene polymorphisms and pathophysiology of bronchial asthma
| Project/Area Number |
09470144
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Fukushima Medical University (1999)
Hokkaido University (1997-1998) |
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Principal Investigator |
MUNAKATA Mitsuru Fukushima Medical University, Department of Pulmonary Medicine, Prof., 医学部, 教授 (00209991)
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| Co-Investigator(Kenkyū-buntansha) |
KAWAKAMI Yoshikazu Hokkaido Univ. First Dept. of Med., Prof., 医学部, 教授 (10001877)
YAMAGUCHI Etsuro Hokkaido Univ. First Dept. of Med., Lecturer, 医学部付属病院, 講師 (10201831)
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| Project Period (FY) |
1997 – 1999
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| Keywords | bronchial asthma / molecular pathophysiology / polymorphism / β2-adrenoceptor / regular inhalation therapy / c-AMP / racial difference |
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| Research Abstract |
2. With the established ARMS methods, genotypes of 150 healthy controls and 178 asthmatics. However, in asthmatics, Gly16/Gly16 genotype was related to the severity of asthma and the use of methylxanthin in their treatment. In addition, there was a significant racial differences in methylxanthin in their treatment. In addition, there was a significant racial differences in genotypes. In Japanese, Glu27/Glu27 genotype is extremely rare and only 1% of population has this genotype.
Relationships between β2-adrenergic receptor gene polymorphisms and pathophysiology of bronchial asthma were examined and the following results were obtained.
1. The ARMS method for the determination of genotype of nucleotide 46, 79 and 523 was established by applying both sequence specific PCR and direct sequencing with di-deoxi method.
3. Isoproterenol induced c-AMP response of peripheral mononuclear (PMN) cells were examined. There was no difference in ECィイD250ィエD2 among nucleotide 46 genotype (Arg16 or Gly16), however, Gly16/Gly16 genotype showed relatively weak maximum response compared to other genotypes (P<0.1).
4. The effects of 2 weeks-regular inhalational therapy with β2-agonist were examined in 19 asthmatic patients. Patients with Gly16/Gly16 genotype showed significant decrease in baseline FEV1, PCィイD220ィエD2-methacholine and c-AMP responses to inhaled salbutamol after treatment, suggesting that receptor down-regulation may be induced after long-term β2-agonist therapy and may cause worsening of asthma in this genotype.
These results suggest that β2-adrenergic receptor gene polymorphisms are one of the genetic background which modify the clinical characteristics of bronchial asthma and the effectiveness of β2-agonist treatment.
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