Variant Aldehyde Dehydrogenase 2 (ALDH2*2) Is a Risk Factor for Coronary Spasm and ST-Segment Elevation Myocardial Infarction

J Am Heart Assoc. 2016 May 6;5(5):e003247. doi: 10.1161/JAHA.116.003247.

Abstract

Background: Mitochondrial aldehyde dehydrogenase 2 (ALDH2) plays a key role in removing toxic aldehydes. Deficient variant ALDH2*2 genotype is prevalent in up to 40% of the East Asians and reported to be associated with acute myocardial infarction (AMI). To elucidate the mechanisms underlying the association of ALDH2*2 with AMI, we compared the clinical features of AMI patients with ALDH2*2 to those with wild-type ALDH2*1/*1.

Methods and results: The study subjects consisted of 202 Japanese patients with acute ST-segment elevation myocardial infarction (STEMI) (156 men and 46 women; mean age, 67.3±12.0) who underwent primary percutaneous coronary intervention (PCI). In 85 patients, provocation test for coronary spasm was also done 6 month post-PCI. ALDH2 genotyping was performed by direct application of the TaqMan polymerase chain system. Of the 202 patients, 103 (51.0%) were carriers of ALDH2*2 and 99 (49.0%) those of ALDH2*1/*1. There were no differences in clinical features between ALDH2*2 and ALDH2*1/*1 carrier groups except higher frequencies of coronary spasm and alcohol flush syndrome (AFS) (88.6% vs 56.1%; P=0.001 and 94.3% vs 17.6%; P<0.001), less-frequent alcohol habit (14.6% vs 51.5%; P<0.001), and higher peak plasma creatine phophokinase levels (2224 vs 1617 mg/dL; P=0.002) in the ALDH2*2 than the ALDH2*1/*1 carrier group.

Conclusions: ALDH2*2 is prevalent (51.0%) among Japanese STEMI patients, and those with ALDH2*2 had higher frequencies of coronary spasm and AFS and more-severe myocardial injury compared to those with ALDH2*1/*1.

Keywords: acute myocardial infarction; alcohol flushing syndrome; aldehyde dehydrogenase 2; coronary spasm; coronary spastic angina.

MeSH terms

  • Aged
  • Aldehyde Dehydrogenase, Mitochondrial / genetics*
  • Asian People
  • Central Nervous System Depressants / adverse effects
  • Coronary Vasospasm / genetics*
  • Creatine Kinase / blood
  • Ethanol / adverse effects
  • Female
  • Flushing / chemically induced
  • Flushing / genetics
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Genotype
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Percutaneous Coronary Intervention
  • Risk Factors
  • ST Elevation Myocardial Infarction / blood
  • ST Elevation Myocardial Infarction / genetics*
  • ST Elevation Myocardial Infarction / surgery
  • Severity of Illness Index
  • Troponin T / blood

Substances

  • Central Nervous System Depressants
  • Troponin T
  • Ethanol
  • ALDH2 protein, human
  • Aldehyde Dehydrogenase, Mitochondrial
  • Creatine Kinase