| Project/Area Number |
13670585
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | HOKKAIDO UNIVERSITY |
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Principal Investigator |
HIZAWA Nobuyuki Hokkaido University Hospital, Instructor, 医学部附属病院, 講師 (00301896)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAGUCHI Etsuro Hokkaido University, Graduate School of Medicine, Associate Professor, 大学院・医学研究科, 助教授 (10201831)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2001: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Asthma / Atopy / CTLA4 / RANTES / MIF / NOS2 / アトピー / No / No合成酵素 |
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| Research Abstract |
We recently established that the -109 C/T promoter polymorphism at FCER1B is a generic factor that affects total serum IgE levels. The genes encoding cytotoxic T lymphocyte antigen-4 (CTLA4) and nitric oxide (NO) are another candidate factors in high IgE responsiveness The CC chemokine RANTES attracts eosinophils, basophils and T cells during inflammation and immune response, indicating a role for this chemokine in asthma. We performed a case-control study with 339 asthmatic patients and 305 healthy controls to investigate the genetic influence of these genes on the development of asthma and atopy. Asthmatic patients who were homozygous for the CTLA4 -318C allele had higher levels of total serum IgE than asthmatic patients carrying the CTLA4 -318T allele (p=0.00470). The analysis of -318C/T (at CTLA4) and -109C/T (at FCER1B) promoter polymorphisms showed a significant correlation between the combined genotypes and increased levels of total IgE in asthmatic patients (p=0.000014). The NOS2 14-repeat allele was inversely associated with atopy (OR=0.42, p<0.01). The RANTES -28G allele was significantly associated with late-onset asthma (OR=2.033 [95%CI, 1.379-2.998], p<0.0025). Further evidence of the importance of the RANTES -28G allele was a significant increase in the production of RANTES in vitro in individuals who carried this allele. Our findings suggest that promoter polymorphisms of both CTLA4 and FCER1B are genetic factors that influence total serum IgE levels in asthmatic patients. This supports the theory that variance in total serum IgE levels in asthmatic patients is determined by mutations in multiple genes, each of which has a relatively small effect on the phenotype. Our findings also suggest that the NOS2 (CCTTT)_n repeat polymorphism is a risk factor for the development of atopy. Among Japanese, the -28G allele of the RANTES promoter region also confers susceptibility to late-onset asthma.
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