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

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K10190
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Embryonic/Neonatal medicine
• Research Institution: Jichi 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
• Keywords: 低出生体重児 / ストレス / メチル化 / 発達障害

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.

Free Research Field

新生児医学

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。