| Project/Area Number |
11670740
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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 |
Pediatrics
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| Research Institution | CHIBA UNIVERSITY |
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Principal Investigator |
TERAI Masaru Chiba University, Graduate School of Medicine, Lecturer, 大学院・医学研究院, 講師 (80207472)
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| Co-Investigator(Kenkyū-buntansha) |
JIBIKI Toshiaki Teikyo University, Ichihara Hospital, Assistant, 医学部・附属市原病院, 助手 (80235796)
OANA Shinji Chiba University, Graduate School of Medicine, Assistant, 大学院・医学研究院, 助手 (80292704)
浜田 洋通 千葉大学, 医学部・附属病院, 医員
山本 重則 千葉大学, 医学部, 助手 (30241970)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Kawasaki disease / MCP-1 / Polymorphism / Kawasaki disease / VEGF / 川崎病 |
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| Research Abstract |
Kawasaki disease (KD) is an acute febrile vasculitic syndrome of unknown etiology preferentially affecting Japanese children. In this project, we reported an enhanced expression of MCP-1 in the coronary vessels infiltrated by macrophages in fatal KD, suggesting a role of MCP-1 in the pathogenesis of KD.
Recently, the polymorphism at position -2518 (G or A), relative to the major transcriptional start site of the MCP-1 gene, was shown to influence the level of MCP-1 production in response to interleukin 1β in vitro (Rovin et al). We reproduced this in vitro effect of MCP-1 production using 18 Japanese healthy volunteers. PBMC from Japanese individuals who carry the -2518 G allele(high production of MCP-1) produced more MCP-1 than hoinozygotes for the A allele (low production of MCP-1) (p<0.01 by unpaired Welch's t test), consistent with an earlier study.
The A allele was found to be predominant among Caucasian and African American populations, suggesting a possible ethnic variation. The G/A polymorphism in Japanese population has not been investigated. Informed consent for this study was obtained from all subjects before the study. The observed genotype and allele frequencies showed that G allele (high production of MC-1 was largely predominant among the Japanese population. The frequency of the A allele was 35 % and that of the G allele was 65 %. In addition, the serum levels of MCP-1 in KD patients with G allele were higher than those in homozygotes for the A allele, although the statistical significance was not obtained when tested by Mann-Whitney U test (p = 0.24). In conclusion, the high prevalence of G allele in the distal regulatory region of the MCP-1 gene in Japanese may suggest a potentially important ethnic variation in the regulation of MCP-1 production, which may contribute to the pathogenesis of KD.
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