East Asians Variant Mitochondrial Aldehyde Dehydrogenase 2 Genotype Exacerbates Nitrate Tolerance in Patients With Coronary Spastic Angina

Mizuno, Yuji; Harada, Eisaku; Kugimiya, Fumihito; Shono, Masayuki; Kusumegi, Izumi; Yoshimura, Michihiro; Kinoshita, Kenji; Yasue, Hirofumi

doi:10.1253/circj.cj-19-0989

Cited by 10 publications

(6 citation statements)

References 47 publications

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“…It is well known that coronary artery spasm provocation tests (e.g., the acetylcholine challenge test, hyperventilation test, and ergometrine challenge test) can help diagnose variant angina pectoris 10 . Further research is needed regarding atherosclerotic plaque and vascular spasm in variant angina patients with severe arrhythmia, including those with Type II second‐degree and III AV block, especially regarding underlying coronary artery spasm‐related gene polymorphisms (e.g., endothelial nitric oxide synthase gene), 11 the clinical progression, and clinical implications.…”

Section: Discussionmentioning

confidence: 99%

Recurrent syncope driven by unique‐variant angina pectoris

Yang,

Lei,

Xin

et al. 2024

Clinical Case Reports

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Section: Discussionmentioning

confidence: 99%

Recurrent syncope driven by unique‐variant angina pectoris

Yang,

Lei,

Xin

et al. 2024

Clinical Case Reports

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“…Studies of the effects of ALDH2 on nitroglycerin mainly focused on coronary artery disease, such as myocardial infarction, coronary heart disease, and coronary artery spasm. Hirofumi Yasue et al found ALDH2*2 attenuated GTN response and exacerbated GTN tolerance in coronary spasm patients [ 23 ]. Li Jin et al found that the presence of the Lys504 allele of ALDH2 contributes in part to the failure of the efficacious response to nitroglycerin in coronary heart disease [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

The effects of ALDH2 Glu487Lys polymorphism on vasovagal syncope patients undergoing head-up tilt test supplemented with sublingual nitroglycerin

Xia

Jin

et al. 2022

BMC Cardiovasc Disord

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Background and objective Head-up tilt test (HUTT) is clinically advantageous for diagnosing patients with vasovagal syncope (VVS). Nitroglycerin is mainly used as a stimulant during HUTT, and mitochondrial aldehyde dehydrogenase 2 (ALDH2) is involved in the metabolism of nitroglycerin (NTG). ALDH2 Glu487Lys polymorphism (ALDH2 rs671) is the most common variant in the East Asian population. This study aimed to assess the effects of ALDH2 rs671 on VVS patients undergoing HUTT supplemented with sublingual NTG (HUTT-NTG). Methods Patients with recurrent VVS (at least 2 times) who were admitted to the syncope center of our hospital were enrolled. All VVS patients have undergone HUTT. The polymorphism of Glu487Lys gene of ALDH2 was measured by the DNA Microarray Chip Method. The results of HUTT-NTG of VVS patients with different ALDH2 genotypes were compared and their hemodynamic characteristics were assessed. Results A total of 199 VVS patients were enrolled, including 101 patients in the ALDH2*1/*1 group and 98 patients in the ALDH2*2 group. Among patients undergoing HUTT-NTG, 70.3% of patients in the ALDH2*1/*1 group and 68.4% of patients in the ALDH2*2 group were positive, and the difference between the two groups was not statistically significant (P = 0.77). The proportions of VASIS I, VASIS II, and VASIS III were 40.6%, 8.9%, and 20.8% in the ALDH2*1/*1 group, respectively, and the corresponding proportions in the ALDH2*2 group were 36.7%, 11.2%, and 20.4%, respectively. There was no statistically significant difference between the two groups (P = 0.91). The hemodynamic characteristics of different genotypes in VVS patients undergoing HUTT-NTG were compared, and no statistically significant difference was found. The median time of syncopal episode occurred after NTG administration in the ALDH2*1/*1 group was 6 min (interquartile range [IQR]: 5.0–9.0), and it was 6.0 min in the ALDH2*2 group (IQR: 4.25–8.0, P = 0.64). Conclusion ALDH2 Glu487Lys polymorphism did not affect the outcome of VVS patients undergoing HUTT-NTG, and no significant change in the hemodynamic characteristics of different genotypes was found.

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“…205,211 Thus, carriers of ALDH2 * 2 are less responsive to nitroglycerin, more prone to nitroglycerin tolerance, and more susceptible to increased ROS. 212,213 Although racial differences in the incidence of CSA have not yet been fully investigated, it is generally believed that it is more common in East Asians than in Westerners. 8, 201 The reason for this is unclear, but may be explained by the high prevalence of ALDH2*2 and high smoking rates among East Asians.…”

Section: Aldh2 Polymorphism and Alcohol Metabolismmentioning

confidence: 99%