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Vasodilatory effect of nitroglycerin in Japanese subjects with different aldehyde dehydrogenase 2 (ALDH2) genotypes.
Chem Biol Interact. 2017 Oct 01; 276:40-45.CB

Abstract

The functional genetic polymorphism of aldehyde dehydrogenase 2 (ALDH2) influences the enzymatic activities of its wild type (Glu504 encoded by ALDH2*1) and mutant type (Lys504 encoded by ALDH2*2) proteins. The enzymatic activities of mutant-type ALDH2 are limited compared with those of the wild type. ALDH2 has been suggested as a critical factor for nitroglycerin-mediated vasodilation by some human studies and in vitro studies. Currently, there is no research on direct observations of the vasodilatory effect of nitroglycerin sublingual tablets, which is the generally used dosage form. In the present study, the contribution of ALDH2 to the vasodilatory effect of nitroglycerin sublingual tablets was investigated among three genotype groups (ALDH2*1/*1, ALDH2*1/*2, and ALDH2*2/*2) in Japanese. The results by direct assessments of in vivo nitroglycerin-mediated dilation showed no apparent difference in vasodilation among all genotypes of ALDH2. Furthermore, to analyze the effect of other factors (age and flow-mediated dilation), multiple regression analysis and Pearson's correlation coefficient analysis were carried out. These analyses also indicated that the genotypes of ALDH2 were not related to the degree of vasodilation. These results suggest the existence of other predominant pathway(s) for nitroglycerin biotransformation, at least with regard to clinical nitroglycerin (e.g., a sublingual tablet) in Japanese subjects.

Authors+Show Affiliations

Laboratory of Biochemistry, Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nishikiori-kita, Tondabayashi, Osaka 584-8540, Japan; Pharmaceutical Education Support Center, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, 11-68 Koshien, 9-Bancho, Nishinomiya, Hyogo 663-8179, Japan. Electronic address: tmiura@mukogawa-u.ac.jp.Laboratory of Biochemistry, Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nishikiori-kita, Tondabayashi, Osaka 584-8540, Japan.Laboratory of Biochemistry, Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nishikiori-kita, Tondabayashi, Osaka 584-8540, Japan.Department of Clinical Research, National Hospital Organization Hakodate Hospital, 18-16, Kawahara, Hakodate, Hokkaido 041-8512, Japan.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28342890

Citation

Miura, Takeshi, et al. "Vasodilatory Effect of Nitroglycerin in Japanese Subjects With Different Aldehyde Dehydrogenase 2 (ALDH2) Genotypes." Chemico-biological Interactions, vol. 276, 2017, pp. 40-45.
Miura T, Nishinaka T, Terada T, et al. Vasodilatory effect of nitroglycerin in Japanese subjects with different aldehyde dehydrogenase 2 (ALDH2) genotypes. Chem Biol Interact. 2017;276:40-45.
Miura, T., Nishinaka, T., Terada, T., & Yonezawa, K. (2017). Vasodilatory effect of nitroglycerin in Japanese subjects with different aldehyde dehydrogenase 2 (ALDH2) genotypes. Chemico-biological Interactions, 276, 40-45. https://doi.org/10.1016/j.cbi.2017.03.012
Miura T, et al. Vasodilatory Effect of Nitroglycerin in Japanese Subjects With Different Aldehyde Dehydrogenase 2 (ALDH2) Genotypes. Chem Biol Interact. 2017 Oct 1;276:40-45. PubMed PMID: 28342890.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vasodilatory effect of nitroglycerin in Japanese subjects with different aldehyde dehydrogenase 2 (ALDH2) genotypes. AU - Miura,Takeshi, AU - Nishinaka,Toru, AU - Terada,Tomoyuki, AU - Yonezawa,Kazuya, Y1 - 2017/03/23/ PY - 2016/09/10/received PY - 2017/01/31/revised PY - 2017/03/19/accepted PY - 2017/3/28/pubmed PY - 2017/11/29/medline PY - 2017/3/27/entrez KW - 1, 2-glyceryl dinitrate KW - ADH KW - Aldehyde dehydrogenases KW - FMD KW - GDN KW - GTN KW - Genotype KW - NMD KW - NO KW - Nitroglycerin KW - Nitroglycerin-mediated dilation KW - Vasodilation KW - alcohol dehydrogenases KW - flow-mediated dilation KW - glyceryl trinitrate KW - nitric oxide KW - nitroglycerin-mediated dilation SP - 40 EP - 45 JF - Chemico-biological interactions JO - Chem Biol Interact VL - 276 N2 - The functional genetic polymorphism of aldehyde dehydrogenase 2 (ALDH2) influences the enzymatic activities of its wild type (Glu504 encoded by ALDH2*1) and mutant type (Lys504 encoded by ALDH2*2) proteins. The enzymatic activities of mutant-type ALDH2 are limited compared with those of the wild type. ALDH2 has been suggested as a critical factor for nitroglycerin-mediated vasodilation by some human studies and in vitro studies. Currently, there is no research on direct observations of the vasodilatory effect of nitroglycerin sublingual tablets, which is the generally used dosage form. In the present study, the contribution of ALDH2 to the vasodilatory effect of nitroglycerin sublingual tablets was investigated among three genotype groups (ALDH2*1/*1, ALDH2*1/*2, and ALDH2*2/*2) in Japanese. The results by direct assessments of in vivo nitroglycerin-mediated dilation showed no apparent difference in vasodilation among all genotypes of ALDH2. Furthermore, to analyze the effect of other factors (age and flow-mediated dilation), multiple regression analysis and Pearson's correlation coefficient analysis were carried out. These analyses also indicated that the genotypes of ALDH2 were not related to the degree of vasodilation. These results suggest the existence of other predominant pathway(s) for nitroglycerin biotransformation, at least with regard to clinical nitroglycerin (e.g., a sublingual tablet) in Japanese subjects. SN - 1872-7786 UR - https://www.unboundmedicine.com/medline/citation/28342890/Vasodilatory_effect_of_nitroglycerin_in_Japanese_subjects_with_different_aldehyde_dehydrogenase_2__ALDH2__genotypes_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0009-2797(17)30319-8 DB - PRIME DP - Unbound Medicine ER -