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

BACKGROUND

Aldehyde dehydrogenase 2 (ALDH2) plays a central role in the biotransformation of glyceryl trinitrate (GTN) or nitroglycerin, which is widely used for the treatment of coronary artery disease (CAD). The deficient variant ALDH2 genotype (ALDH22) is prevalent among East Asians. This study examined whether there are differences in nitroglycerine-mediated dilation (NMD) and flow-mediated dilation (FMD) response between wildALDH21/1and variantALDH22patients with CAD.

METHODS AND RESULTS

The study subjects comprised 55 coronary spastic angina (CSA) patients, confirmed by coronary angiography and intracoronary injection of acetylcholine (42 men and 13 women, mean age 68.0±9.0 years). They underwent NMD and FMD tests in the morning before and after continuous transdermal GTN administration for 48 h. NMD was lower at baseline inALDH22than in theALDH21/1group (P=0.0499) and decreased significantly in both groups (P<0.0001 and P<0.0001, respectively) after GTN, with significantly lower levels in theALDH22group (P=0.0002). FMD decreased significantly in bothALDH2*1/1andALDH22groups (P<0.0001and P=0.0002, respectively) after continuous GTN administration, with no significant differences between the 2 groups both before and after GTN.

CONCLUSIONS

Continuous administration of GTN produced endothelial dysfunction as well as nitrate tolerance in bothALDH21/1andALDH22patients with CSA.ALDH22attenuated GTN response and exacerbated GTN tolerance, but not endothelial dysfunction, as compared toALDH21/*1in patients with CSA.