Pharmacogenetic studies on the influence of ALDH2 gene polymorphisms on the vasodilation induced by organic nitrates

2010 Fiscal Year Final Research Report

• Project/Area Number: 20390160
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: Kyushu University
• Principal Investigator: SASAGURI Toshiyuki Kyushu University, 大学院・医学研究院, 教授 (30261209)
• Co-Investigator(Kenkyū-buntansha): TAKAHASHI Fumi 九州大学, 大学院・医学研究院, 助教 (50274436) ; MATSUMURA Kiyoshi 九州大学, 病院, 助教 (70285469)
• Project Period (FY): 2008 – 2010
• Keywords: 硝酸薬 / ニトログリセリン / 二硝酸イソソルビド / 狭心症 / 血管拡張 / 2型アルデヒド脱水素酵素 / 遺伝子多型 / ゲノム薬理学

Research Abstract

To examine whether polymorphisms at codon 487 of aldehyde dehydrogenase 2 (ALDH2) influence nitroglycerin (GTN)-induced vasodilation, and whether GTN or isosorbide dinitrate (ISDN) is more effective in each genotype, we performed a crossover trial using sublingual spray of GTN and ISDN. Maximal artery diameter increase in response to GTN or ISDN did not differ among genotypes. However, the time required for dilation was longer in the ^*1/^*2 and ^*2/^*2 genotypes than ^*1/^*1. In contrast, ISDN-induced dilation did not differ among genotypes. The time required for GTN dilation was shorter than that for ISDN dilation among ^*1 allele carriers, whereas GTN and ISDN dilation did not differ among participants carrying ^*2/^*2. These results suggested that the response to GTN was significantly delayed in ^*2 allele carriers. GTN dilated the artery more quickly than ISDN in ^*1/^*1 and ^*1/^*2, but not in ^*2/^*2.

Research Products

• [Journal Article] Differential effects of organic nitrates on arterial diameter among healthy Japanese participants with different mitochondrial aldehyde dehydrogenase 2 genotypes : randomised crossover trial. (2011)
  • Author(s): Sakata S, Yoshihara T, Arima H, Shiraishi F, Oniki H, Takahashi-Yanaga F, Matsumura K, Sasaguri T.
  • Journal Title: BMJ Open in press.
• [Presentation] 2型アルデヒド脱水素酵素の遺伝子多型ガニトログリセリンおとび二硝酸イソソルビドの血管拡張作用に印ぼす効果 (2010)
  • Author(s): 吉原達也, 坂田智子, 白石富美恵, 鬼木秀幸, 市島久仁彦, 大坪俊夫, 三輪宜一, 高橋富美, 有馬久富, 松村潔, 笹栗俊之
  • Organizer: 第31回日本臨床薬理学会年会
  • Place of Presentation: 京都
  • Year and Date: 20101201-20101203
• [Presentation] ALDH2の遺伝子多型がニトログリセリンの薬効に印ぼす影響 (2010)
  • Author(s): 笹栗俊之, 坂田智子, 吉原達也, 白石富美恵, 松村潔
  • Organizer: 第20回日本循環薬理学会年会
  • Place of Presentation: 札幌
  • Year and Date: 20101111-20101112
• [Presentation] 2型アルデヒド脱水素酵素の遺伝子多型がニトログリセリンおよび二硝酸イソソルビドの血管拡張作用に及ぼす影響 (2010)
  • Author(s): 坂田智子, 松村潔, 三輪宜一, 鬼木秀幸, 市島久仁彦, 吉原達也, 高橋富美, 白石富美恵, 大坪俊夫, 笹栗俊之
  • Organizer: 第33回日本高血圧学会年会
  • Place of Presentation: 福岡
  • Year and Date: 20101015-20101017
• [Presentation] Effect of aldehyde dehydrogenase-2 gene polymorphism on vasodilatory response of brachial artery induced by nitroglycerin. (2010)
  • Author(s): Sakata S, Matsumura K, Miwa Y, Oniki H, Ichishima K, Arima H, Takahashi-Yanaga F, Yoshihara T, Shiraishi F, Iida M, Sasaguri T
  • Organizer: 23rd Scientific Meeting of the International Society of Hypertension
  • Place of Presentation: バンクーバー
  • Year and Date: 20100926-20100930
• [Presentation] Influence of aldehyde dehydrogenase-2 gene polymorphism on vasodilatation induced by organic nitrates in healthy human subjects. (2010)
  • Author(s): Sakata S, Ichijima K, Oniki H, Miwa Y, Arima H, Matsumura K, Yoshihara T, Takahashi-Yanaga F, Shiraishi F, Sasaguri T
  • Organizer: WorldPharma 2010
  • Place of Presentation: コペンハーゲン
  • Year and Date: 20100717-20100723
• [Book] NEW薬理学(改訂第6版)(抗狭心症薬) (2011)
  • Author(s): 笹栗俊之
  • Total Pages: 395-399
  • Publisher: 南江堂