2000 Fiscal Year Final Research Report Summary
Identification of Genes for High IgE responsiveness in Chromosomes 5q31 and 11q13
| Project/Area Number |
10307013
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| Research Category |
Grant-in-Aid for Scientific Research (A).
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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 |
YAMAGUCHI Etsuro Hokkaido University Hospital, First Department of Medicine, Assistant Professor, 医学部・附属病院, 講師 (10201831)
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| Co-Investigator(Kenkyū-buntansha) |
NASUHARA Yasuyuki Hokkaido University Hospital, First Department of Medicine, Instructor, 医学部・附属病院, 助手 (30322811)
ITOH Akihide Hokkaido University Hospital, First Department of Medicine, Instructor, 医学部・附属病院, 助手 (30291230)
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| Project Period (FY) |
1998 – 2000
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| Keywords | high affinity IgE Fc receptor / IL-4 / atopy / bronchial asthma / atopic dermatitis / IgE / single nucleotide polymorphism |
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| Research Abstract |
(1) We found a C to T change, novel single nucleotide polymorphism at position -109 in the promoter region of high affinity receptor for Fc portion of IgE.There was no significant difference in the distribution of this polymorphism between patients with asthma and healthy controls. However, asthmatic patients homozygous for allele T had significantly higher total serum IgE levels (p=0.0015) than those with other genotypes (TC or CC). When ages at asthma onset were taken into account, the effects polymorphism on serum total IgE became more evident (p=0.0004).
(2) We have also found a novel polymorphism (+33C/T) in the untranslated region of the IL-4 gene. The allele frequencies of T in asthmatic patients and healthy controls were 0.675 and 0.671, respectively, and there was no significant difference between the two groups. Meanwhile, individuals with genotype CT or CC in all study subjects or asthmatic patients had significantly higher serum total IgE levels, even when corrected for sex
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and ages compared with those with genotype CC.
(3) We analyzed the interaction of two aforementioned single nucleotide polymorphisms (SNP) on serum total IgE levels. The effects of the two SNP in asthmatic patients seemed to be dependent on genotypes of each SNP.
(4) We found no significant differences in the frequencies of two aforementioned SNP between patients with atopic dermatitis and healthy controls, thus indicating that these gene polymorphisms did not contribute to the development of the disease. Also, the two SNP did not correlate with serum total IgE levels in patients with atopic dermatitis. Therefore, we concluded that gene polymorphisms or environmental factors other than genes for high affinity IgE Fc receptor or IL-4 had greater impact on the interindividual differences in increased levels of serum total IgE in patients with atopic dermatitis.
(5) We have found SNPs without amino acid changes at positions 287 and 1353 downstream from a translation initiation site of the muscarinic receptor M1 gene. A case-control study on the polymorphisms revealed that the frequency of genotype CC in patients with asthma was significantly higher than healthy controls, thus suggesting that M1 receptor gene may affect the occurrence of asthma independently of atopy. Less
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