2022 Fiscal Year Final Research Report
A molecular epidemiological study of associations between autism spectrum disorders induced by prenatal dioxin exposure and alteration of clock gene expressions
| Project/Area Number |
17H04665
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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 | 海外学術 |
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| Research Field |
Hygiene and public health
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| Research Institution | Kanazawa Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
田崎 隆史 金沢医科大学, 総合医学研究所, 准教授 (70629815)
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| Project Period (FY) |
2017-04-01 – 2022-03-31
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| Keywords | ダイオキシン / クロックジーン / 睡眠時間 / 攻撃性 / ADHD / 学習障害 / 周産期曝露 |
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| Outline of Final Research Achievements |
To investigate effects of perinatal dioxin exposure on circadian rhythm, clock gene RNA expression of buccal mucosa swaps was examined in 9-year-olds from Da Nang birth cohort recruited in 2007-8 living around former Da Nang U.S. airbase. A total 135 children were participated to the survey, BMAL1 RNA expression was detected in 17 boys and 15 girls. In girls with detected BMAL1, increased BMAL1 copy number was associated with increasing TCDD and TEQ-PCDD/Fs. Also, inverse correlations were found between BMAL1 copy number and sleep hours at night and total sleep hours including nap time in girls. Increased CLDQ language score in boys and hyperactivity impulsiveness score in girls were also significantly correlated with increased BMAL1 copy number.
When we performed similar analysis in 56 boys and 36 girls whose Per 1 RNA gene expression were detected and found that Per1 copy number decreased with increasing TEQ-PCDD/Fs and increased with increasing verbal aggression and hostility scores.
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| Free Research Field |
環境保健
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、高TCDD曝露によるADHD症状、特に多動・衝動性の増加がクロックジーン、特にBMAL1の日中での発現と関連していることを報告した。このことは、周産期ダイオキシン曝露による発達障害増加の分子生物学的メカニズムの一端を示すことができたと考えられる。また、BMAL1は日内リズムに関与しているだけでなく、老化やアルツハイマー病やパーキンソン病などの神経疾患発症においても重要な役割を果たしていることが報告されている。
近年、ベトナム戦争に従軍したアメリカ人退役軍人の調査でも、枯葉剤曝露によるアルツハイマー病の発症リスク増加が示唆されており、BMAL1が有用な健康指標となる可能性がある。
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