ArticleThe Journal of clinical investigation2006
Mitochondrial aldehyde dehydrogenase-2 (ALDH2) Glu504Lys polymorphism contributes to the variation in efficacy of sublingual nitroglycerin.
Article in The Journal of clinical investigation, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Meta-Analysis on the Association of ALDH2 Polymorphisms and Type 2 Diabetic Mellitus, Diabetic Retinopathy.International journal of environmental research and public health · 2017Pooled it
- Influence of the aldehyde dehydrogenase 2 polymorphism on the vasodilatory effect of nitroglycerin in infants with congenital heart disease and pulmonary arterial hypertension.European journal of clinical pharmacology · 2019Trial
- Mechanisms and preventive measures of ALDH2 in ischemia‑reperfusion injury: Ferroptosis as a novel target (Review).Molecular medicine reports · 2025Review
- Geographical distribution of ALDH2 rs671 polymorphism in Chinese angina pectoris patients.Frontiers in genetics · 2025Article
- Advances in Factors Affecting ALDH2 Activity and its Mechanisms.Cardiovascular toxicology · 2024Review
- Analysis of Correlation Between Coronary Heart Disease and Genetic Polymorphism Detected by Gold Magnetic Nanoparticles Chromatography.Journal of cardiovascular translational research · 2024Article
- Rapid and accurate genotyping of human SNP rs671 in aldehyde dehydrogenase 2 gene using one-step CRISPR/Cas12b assay without DNA amplification.Cell division · 2023Article
- The role of aldehyde dehydrogenase 2 in cardiovascular disease.Nature reviews. Cardiology · 2023Review
- Nitroglycerin: a comprehensive review in cancer therapy.Cell death & disease · 2023Review
- p53 protects against alcoholic fatty liver disease via ALDH2 inhibition.The EMBO journal · 2023Article
- The effects of ALDH2 Glu487Lys polymorphism on vasovagal syncope patients undergoing head-up tilt test supplemented with sublingual nitroglycerin.BMC cardiovascular disorders · 2022Article
- Genetic Variations of ALDH (rs671) Are Associated With the Persistence of HBV Infection Among the Chinese Han Population.Frontiers in medicine · 2022Article
- Glyceryl Trinitrate: History, Mystery, and Alcohol Intolerance.Molecules (Basel, Switzerland) · 2021Review
- Origin and Spread of the ALDH2 Glu504Lys Allele.Phenomics (Cham, Switzerland) · 2021Review
- Diabetic Aldehyde Dehydrogenase 2 Mutant (ALDH2*2) Mice Are More Susceptible to Cardiac Ischemic-Reperfusion Injury Due to 4-Hydroxy-2-Nonenal Induced Coronary Endothelial Cell Damage.Journal of the American Heart Association · 2021Article
- Acetaldehyde Enhances Alcohol Sensitivity and Protects against Alcoholism: Evidence from Alcohol Metabolism in Subjects with VariantBiomolecules · 2021Article
- [Pharmacogenomics: precision tool in routine prescription].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2020Article
- ALDH2 genotype modulates the association between alcohol consumption and AST/ALT ratio among middle-aged Japanese men: a genome-wide G × E interaction analysis.Scientific reports · 2020Article
- Aldehyde Dehydrogenase 2 Ameliorates Chronic Alcohol Consumption-Induced Atrial Fibrillation through Detoxification of 4-HNE.International journal of molecular sciences · 2020Article
- Novel and prevalent non-East Asian ALDH2 variants; Implications for global susceptibility to aldehydes' toxicity.EBioMedicine · 2020Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
Glyceryl trinitrate (GTN), also known as nitroglycerin, has been used to treat angina and heart failure for more than 130 years. Recently, it was shown that mitochondrial aldehyde dehydrogenase-2 (ALDH2) is responsible for formation of NO, the metabolite needed for GTN efficacy. In the present study, we show that the common G-to-A polymorphism in exon 12 of ALDH2--resulting in a Glu504Lys replacement that virtually eliminates ALDH2 activity in both heterozygotes and homozygotes--is associated with a lack of efficacy of sublingual GTN in Chinese subjects. We also show that the catalytic efficiency (Vmax/Km) of GTN metabolism of the Glu504 protein is approximately 10-fold higher than that of the Lys504 enzyme. We conclude that the presence of the Lys504 allele contributes in large part to the lack of an efficacious clinical response to nitroglycerin; we recommend that this genetic factor be considered when administering nitroglycerin to patients, especially Asians, 30-50% of whom possess the inactive ALDH2*2 mutant allele.
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