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DNA methylation levels of stress-response related genes and behavior development in low birth weight infants

Research Project

Project/Area Number 17K10190
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Embryonic/Neonatal medicine
Research InstitutionJichi Medical University

Principal Investigator

Kono Yumi  自治医科大学, 医学部, 教授 (50243390)

Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords低出生体重児 / ストレス / メチル化 / 発達障害 / 早産 / ストレス反応 / 早産児
Outline of Final Research Achievements

To investigate mechanism of behavior developmental disorder in very low birth weight (VLBW) infants, we investigate DNA methylation of human glucocorticoid receptor gene (NR3C1) and serotonin transporter gene (SLC6A4) in cord blood of preterm VLBW infants. Methylation levels at 10 CpG sites in NR3C1 exon 1F and those at 20 CpG sites in SLC6A4 exon 1a were quantified using a pyrosequencing method. The mean methylation levels of NR3C1 were negatively correlated to BW (r= -0.477). The mean methylation levels of SLC6A4 were negatively correlated to gestational age (GA) (r= -0.410). Correlation of methylation levels between NR3C1 and SLC6A4 were not significant. Either methylation of NR3C1 or SLC6A4 did not correlated with maternal smoking, mental disorder, or prenatal steroid use. Thus, methylation levels of NR3C1 and SLC6A4, which could control stress-response were related to lower BW or smaller GA and they may affect to stress-related behavior regulation in later life of VLBW infants.

Academic Significance and Societal Importance of the Research Achievements

早産低出生体重児の臍帯血を用いてストレス反応関連遺伝子であるGR遺伝子、セロトニントランスポーター遺伝子のメチル化率を同時解析し、出生体重、在胎期間との関連が明らかとなった。早産低出生体重を生じるような子宮内ストレスが関連遺伝子のメチル化変化を介して発現制御を変容させ、将来の精神行動発達に影響する可能性が示唆された。対象数が少なく出生体重、在胎期間以外の要因とは有意な関係を認めなかった点は研究の限界であり、また長期の行動発達の観察が必要であるが、本結果は早産低出生体重児の行動発達特性の発症メカニズムおよび病態解明に寄与するものと考える。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (3 results)

All 2020 2019 2018

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (1 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] Neurodevelopmental outcomes of very low birth weight infants in the Neonatal Research Network of Japan: Importance of NICU graduate follow-up.2020

    • Author(s)
      Kono Y
    • Journal Title

      Clin Exp Pediatr.

      Volume: - Issue: 7 Pages: 313-321

    • DOI

      10.3345/cep.2020.01312

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] hanges in survival and neurodevelopmental outcomes of infants born at <25 weeks’ gestation: a retrospective observational study in tertiary centers in Japan.2018

    • Author(s)
      Kono Y, Yonemoto N, Nakanishi H, Kusuda S, Fujimura M
    • Journal Title

      BMJ Paediatr Open

      Volume: 2 Issue: 1 Pages: e000211-e000211

    • DOI

      10.1136/bmjpo-2017-000211

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Survival and neurodevelopmental outcomes of infants born at less than 25 weeks' gestation in the Neonatal Research Network of Japan2019

    • Author(s)
      Yumi Kono
    • Organizer
      the 69th Korean Pediatric Society Annual Congress
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited

URL: 

Published: 2017-04-28   Modified: 2022-01-27  

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