East Asian variant aldehyde dehydrogenase type 2 genotype exacerbates ischemia/reperfusion injury with ST-elevation myocardial infarction in men: possible sex differences.

Mitochondrial aldehyde dehydrogenase 2 (ALDH2) detoxifies toxic aldehydes generated during ischemia/reperfusion (I/R) injury in ST-elevation myocardial infarction (STEMI). The deficient variant ALDH2 genotype (ALDH2*2) is prevalent among East Asians. Whether ALDH2*2 exacerbates I/R injury of in patients with STEMI is not known. The study subjects comprised 218 Japanese patients with STEMI (158 men and 60 women, mean age 67.9 ± 11.9) who underwent successful percutaneous coronary intervention. Of these, 120 (55.0%) were the carriers of variant ALDH2*2 and 98 (45.0%) those of wild ALDH2*1/*1 on genotyping. There were no differences in clinical characteristics between the ALDH2*2 and ALDH2*1/*1 group except lower alcohol habit (14.2% vs 46.3%, P < 0.001) in the ALDH2*2 group. The peak plasma levels of creatine phosphokinase myocardial binding (CKMB), a marker of myocardial injury, however, were significantly higher in the patients with ALDH2*2 than in those with ALDH2*1/*1 [a median 275.0 (175.8-407.5) vs 177.5 (126.9-344.3) U/L, P = 0.001] among men but not among women (P = 0.811). There was a significant interaction between men (male sex) and ALDH2*2 for I/R injury (χ2 = 4.425, P = 0.040). The variant ALDH2*2 was associated with more severe I/R injury than the wild ALDH2*1/*1 in STEMI patients in men with possible sex differences.