East Asian variant aldehyde dehydrogenase Type 2 genotype exacerbates myocardial ischemia/reperfusion injury in men among patients with ST-segment elevation myocardial infarction -sex differences-

Abstract

Abstract Background Mitochondrial aldehyde dehydrogenase 2 (ALDH2) detoxifies toxic aldehydes including those generated during ischemia/reperfusion (I/R) injury in acute myocardial infarction. The deficient variant ALDH2 genotype (ALDH2*2) is prevalent among East Asians. We examined whether ALDH2*2 exacerbates I/R injury in Japanese patients with acute ST-segment elevation myocardial infarction (STEMI) utilizing Mendelian randomization. Methods and results The study subjects comprised 248 Japanese patients with STEMI (187 men and 61 women, mean age 67.1±11.5) who underwent successful primary percutaneous coronary intervention. Of these patients, 129 (52.0%) were the carriers of ALDH2*2 and 119 (48.0%) those of wild ALDH2*1/*1 on genotyping by direct application of the TaqMan polymerase chain system. There were no differences in clinical characteristics between the ALDH2*2 and ALDH2*1/*1 group except lower alcohol habit in the ALDH2*2 group. However, the peak plasma levels of creatine phosphokinase myocardial binding (CKMB), a marker of myocardial injury, were significantly higher (a median 234.0 vs 150.0 U/L, P<0.001 in the ALDH2*2 group. Furthermore, the peak CKMB levels were higher in ALDH2*2 group in men (a median 2 75.0 vs 144.9 U/L, P<0.001) but not in women (P=0.855) and there was a significant interaction between sex and ALDH2*2 on I/R injury (χ2=8.362, P=0.004). Conclusions The peak plasma levels of CKMB were higher in STEMI patients with ALDH2*2 than in those with ALDH2*1/*1 among men but not women. These findings identified deficient ALDH2 activity to be targeted for treatment of STEMI specifically in men with ALDH2*2. Visual overview Funding Acknowledgement Type of funding source: None