Epidemiological study on the origin of lifestyle-related diseases based on epigenetic theory

• Project/Area Number: 15K08802
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hygiene and public health
• Research Institution: Nagoya University
• Principal Investigator: Tamakoshi Koji 名古屋大学, 医学系研究科(保健), 教授 (30262900)
• Project Period (FY): 2015-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: 出生時体重 / 生活習慣病 / エピジェネティクス / DNAメチル化 / 糖尿病 / 家族歴

Outline of Final Research Achievements

Among 421 men (mean 50.7 ± 6.1 years) who had no history of diabetes, hypertension, or abnormal lipid metabolism, the association between birth weight and the methylation of the ATP-binding cassette protein A1 (ABCA1) gene was examined to elucidate the epidemiological pathology of lifestyle-related diseases based on epigenetics theory. The ATP-binding cassette protein A1 (ABCA1) plays an important role in HDL cholesterol production. The methylation rate of DNA was significantly higher in the group of less than 2500 g compared to the group of 2500 g or more among the subjects at age 50 and older, while there was no significant difference between the two groups among those under the age of 50. This finding suggests that the bad prenatal environment may promote the DNA methylation rate of ABCA1 gene in the second half of adulthood.

Academic Significance and Societal Importance of the Research Achievements

これまでの生活習慣病予防対策は、出生以後の生活習慣・環境を良くすることであったが、胎内環境に着目した。胎内環境が高血圧などの生活習慣病の発症に関連することが報告されている。この関連を説明する仕組みの一つとして、胎内環境が遺伝子配列の変化を伴わず、遺伝子の発現のみに変化を与えることが分かっており、その本態は遺伝子のメチル化である。本研究ではHDLコレステロールの生成過程で重要な役割を果たすABCA1遺伝子を取り上げ、良好でない胎内環境が成人期後半における同遺伝子のメチル化率を促進する可能性を明らかにした。公衆衛生的な視点で解釈すると、本研究結果は周産期医療、母子保健の重要性を謳うものである。

Research Products

• [Journal Article] Smoking Results in Accumulation of Ectopic Fat in the Liver (2019)
  • Author(s): Ayako Kato, Yuanying Li, Atsuhiko Ota, Hisao Naito, Hiroya Yamada, Takashi Nihashi, Yo Hotta, Chifa Chiang, Yoshihisa Hirakawa, Atsuko Aoyama, Koji Tamakoshi, Hiroshi Yatsuya
  • Journal Title: Diabetes Metab Syndr Obes Volume: 12 Pages: 1075-1080
  • DOI: 10.2147/dmso.s212495
  • Peer Reviewed / Open Access
• [Journal Article] A Point System for Predicting 10-Year Risk of Developing Type 2 Diabetes Mellitus in Japanese Men: Aichi Workers’ Cohort Study (2018)
  • Author(s): Yatsuya Hiroshi、Li Yuanying、Hirakawa Yoshihisa、Ota Atsuhiko、Matsunaga Masaaki、Haregot Hilawe Esayas、Chiang Chifa、Zhang Yan、Tamakoshi Koji、Toyoshima Hideaki、Aoyama Atsuko
  • Journal Title: Journal of Epidemiology Volume: 28 Issue: 8 Pages: 347-352
  • DOI: 10.2188/jea.JE20170048
  • NAID: 130007431029
  • ISSN: 0917-5040, 1349-9092
  • Year and Date: 2018-08-05
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Association of gamma-glutamyl transferase and alanine aminotransferase with type 2 diabetes mellitus incidence in middle-aged Japanese men: 12-year follow up. (2018)
  • Author(s): Kaneko K, Yatsuya H, Li Y, Uemura M, Chiang C, Hirakawa Y, Ota A, Tamakoshi K, Aoyama A.
  • Journal Title: J Diabetes Investig Volume: - Issue: 3 Pages: 837-845
  • DOI: 10.1111/jdi.12930
  • Peer Reviewed / Open Access
• [Journal Article] Long-term weight-change slope, weight fluctuation and risk of type 2 diabetes mellitus in middle-aged Japanese men and women: findings of Aichi Workers' Cohort Study. (2017)
  • Author(s): Zhang Y, Yatsuya H, Li Y, Chiang C, Hirakawa Y, Kawazoe N, Tamakoshi K, Toyoshima H, Aoyama A.
  • Journal Title: Nutr Diabetes Volume: 7(3) Issue: 3 Pages: e252-e252
  • DOI: 10.1038/nutd.2017.5
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Breakfast Skipping is Positively Associated With Incidence of Type 2 Diabetes Mellitus: Evidence From the Aichi Workers' Cohort Study. (2015)
  • Author(s): Uemura M, Yatsuya H, Hilawe EH, Li Y, Wang C, Chiang C, Otsuka R, Toyoshima H, Tamakoshi K, Aoyama A.
  • Journal Title: J Epidemiol. Volume: 25 Pages: 351-358
  • NAID: 130005067871
  • Peer Reviewed
• [Journal Article] Association between parental history of diabetes and the incidence of type 2 diabetes mellitus differs according to the sex of the parent and offspring's body weight: A finding from a Japanese worksite-based cohort study. (2015)
  • Author(s): Wang C, Yatsuya H, Tamakoshi K, Toyoshima H, Wada K, Li Y, Hilawe EH, Uemura M, Chiang C, Zhang Y, Otsuka R, Ota A, Hirakawa Y, Aoyama A.
  • Journal Title: Prev Med. Volume: 81 Pages: 49-53
  • DOI: 10.1016/j.ypmed.2015.07.021
  • Peer Reviewed
• [Presentation] 特定保健指導レベルと空腹時血糖異常有無による2型糖尿病発症リスク：愛知職域コホート研究 (2020)
  • Author(s): 金子佳世、八谷寛、太田充彦、李媛英、上村真由、江啓発、平川仁尚、玉腰浩司、青山温子
  • Organizer: 第30回 日本疫学会学術集会
• [Presentation] γGTPとALT追加による10年間の2型糖尿病発症リスク予測能の改善 愛知職域コホート (2018)
  • Author(s): 金子 佳世, 八谷 寛, 李 媛英, 上村 真由, 江 啓発, 平川 仁尚, 太田 充彦, 玉腰 浩司, 豊嶋 英明, 青山 温子
  • Organizer: 第77回日本公衆衛生学会総会
• [Presentation] 危険因子の変化を考慮した糖尿病発症リスク予測 (2017)
  • Author(s): 李 媛英, 八谷 寛, 平川 仁尚, 松永 眞章, 太田 充彦, 江 啓発, 張 燕, Haregot Hilawe Esayas, 玉腰 浩司, 豊嶋 英明, 青山 温子
  • Organizer: 第53回日本循環器病予防学会学術集会
• [Presentation] 危険因子の変化を考慮した糖尿病発症リスク予測 (2016)
  • Author(s): 李 媛英, 八谷 寛, 平川 仁尚, 松永 眞章, 太田 充彦, 江 啓発, 張 燕, Haregot Hilawe Esayas, 玉腰 浩司, 豊嶋 英明, 青山 温子
  • Organizer: 第52回日本循環器病予防学会学術集会
  • Place of Presentation: 埼玉県県民健康センター
  • Year and Date: 2016-06-17
• [Presentation] 健診および生活習慣要因による糖尿病発症リスクスコア開発 愛知職域コホート研究 (2015)
  • Author(s): 李 媛英, 八谷 寛, 玉腰 浩司, 上村 真由, 王 超辰, 平川 仁尚, Hilawe Esayas Haregot, 江 啓発, 加藤 善士, 太田 充彦, 張 燕, 豊嶋 英明, 青山 温子
  • Organizer: 第51回日本循環器病予防学会学術集会
  • Place of Presentation: 大阪大学 中之島センター
  • Year and Date: 2015-06-26