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

Background--Mitochondrial aldehyde dehydrogenase 2 (ALDH2) plays a key role in removing toxic aldehydes. Deficient variant ALDH2(star)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(star)2 with AMI, we compared the clinical features of AMI patients with ALDH2(star)2 to those with wild-type ALDH2(star)1/(star)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(star)2 and 99 (49.0%) those of ALDH2(star)1/(star)1. There were no differences in clinical features between ALDH2(star)2 and ALDH2(star)1/(star)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(star)2 than the ALDH2(star)1/(star)1 carrier group. Conclusions-ALDH2(star)2 is prevalent (51.0%) among Japanese STEMI patients, and those with ALDH2(star)2 had higher frequencies of coronary spasm and AFS and more-severe myocardial injury compared to those with ALDH2(star)1/(star)1.