2000 Fiscal Year Final Research Report Summary
Genetic Studies of Allergic Lung Diseases
| Project/Area Number |
11670559
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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, 助手 (00301896)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAGUCHI Etsuro Hokkaido University Hospital, Assistant Professor, 医学部・附属病院, 講師 (10201831)
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| Project Period (FY) |
1999 – 2000
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| Keywords | CCR2-64l / Total serum IgE levels / Sarcoidosis / FCER1B / CTLA4 / Th1 / Th1 balance |
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| Research Abstract |
We investigated the distribution of the CCR2-64l in 100 subjects with sarcoidosis and 122 healthy control subjects. The distribution of the CCR2-64l allele was significantly different between subjects with sarcoidosis and healthy control subjects. The presence of the CCR2-64l allele conferred a lower risk for the development of sarcoidosis. In addition, genetic factors are important in defining total serum IgE levels. A common -109C/T polymorphism at the promoter region of FCER1B was identified, although no variant was found in the entire coding region. Homozygosity for the 109T allele was associated with increased total serum IgE levels in 226 subjects with asthma. The gene encoding cytotoxic T lymphocyte antigen-4 (CTLA4) is another candidate responsible for high IgE responsiveness, because B7-CD28/CTLA-4 interaction can promote the differentiation and development of the Th2 lymphocyte subset. We performed a case-control study using 339 asthmatic patients and 305 healthy controls, which included 226 asthmatics and 219 healthy controls who had been previously studied for the -109C/T promoter polymorphism at FCER1B.Asthmatic patients who were homozygous for the -318C allele at the CTLA4 promoter region had higher levels of total serum IgE than those of patients carrying the -318T allele. The analysis of -318C/T and -109C/T promoter polymorphisms showed a significant correlation between the combined genotypes and increased levels of total IgE in asthmatic patients. Our findings represent genetic heterogeneity and complex interactions between genetic and environmental components involved in the regulation of sarcoidosis and total IgE levels, and support the theory that the Th1/Th1 balance in allergic lung diseases is determined by mutations in multiple genes each of which has a relatively small effect on the phenotype.
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