2000 Fiscal Year Final Research Report Summary
ANALYSIS OF MECHANISMS OF DECREASED CERAMIDE PRODUCTION IN CORNEUM STRATUM PATIENTS WITH ATOPIC DERMATITIS
| Project/Area Number |
11470168
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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 |
Pediatrics
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| Research Institution | GUNMA UNIVERSITY |
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Principal Investigator |
MORIKAWA Akihiro DEPARTMENT OF PEDIATRICS, GUNMA UNIVERSITY SCHOOL OF MEDICINE, PROFESSOR, 医学部, 教授 (40125878)
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| Co-Investigator(Kenkyū-buntansha) |
ARAKAWA Hirokazu DEPARTMENT OF PEDIATRICS, GUNMA UNIVERSITY SCHOOL OF MEDICINE, ASSISTANT, 医学部, 助手 (50272232)
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| Project Period (FY) |
1999 – 2000
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| Keywords | atopic dermatitis / barrier function / TEWL / ceramide / sphingomyelinase / microsatellite / polymorphism / atopic gene |
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| Research Abstract |
1) Impaired barrier function may contribute to the pathophysiology of atopic dermatitis. Ceramides are the main polar lipids of the stratum corneum and play an important role in skin barrier function, cell adhesion and epidermal differentiation. The transepidermal water loss (TEWL), serum IgE and eosinophils count in the peripheral blood were measured in children with atopic dermatitis. The level of TEWL was significantly higher in children with atopic dermatitis than those with bronchial asthma or controls. Neither the level of serum IgE nor eosinophils count were associated with the level of TEWL, suggesting that impaired barrier function is independent of atopic predisposition.
2) To elucidate the mechanisms that are involved in the decrease of ceramide levels in atopic dry ski, we evaluated the possible role of the gene for sphingomyelinase, which is a major enzyme of ceramide production, in modulating atopic dermatitis in the Japanese population. We screened all 6 exons of the sphingomyelinase gene from 5 subjects for mutations by direct polymerase chain reaction (PCR) sequencing. The sphingomyelinase gene polymorphisms were genotyped by PCR fragment length polymorphism analysis. We also evaluated the gene polymorphism for the IL-4 receptor Q576R and STAT6, which is a key transcription factor involved in both IL-4 and IL-13-mediated biological responses. We found a novel dinucleotide repeat polymorphism in the first exon of the sphingomyelinase gene. The genotypes were classified into 6 groups according to the number of hexamer repeats present, from 5 to 11. The frequency of the 7 repeat homozygote was higher in children with atopic dermatitis than controls. This repeat polymorphism was not associated with the polymorphism in the IL-4 receptor (Q576R) and stat6. This suggests that genetic variation in the sphingomyelinase may be associated with predisposition to atopic dermatitis. In addition, this polymorphism may be independent of atopic gene.
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