Pharmacogenetic studies on the influence of ALDH2 gene polymorphisms on the vasodilation induced by organic nitrates

为了验证乙醛脱氢酶2(ALDH2)第487位密码子的多态性是否影响硝酸甘油(GTN)诱导的血管扩张，以及GTN和硝酸异山梨酯(ISDN)在两种基因型中哪个更有效，我们进行了GTN和ISDN舌下喷雾的交叉试验。对GTN或ISDN反应的最大动脉内径增加在不同的基因型之间没有差异。然而，^*1/^*2和^*2/^*2的扩张型所需的时间比^*1/^*1的长。相反，ISDN诱导的扩张性在不同的基因型之间没有差异。在^*1等位基因携带者中，GTN扩张所需的时间比ISDN扩张所需的时间短，而在携带^*2/^*2等位基因的受试者中，GTN和ISDN扩张所需的时间没有差异。这些结果表明^*2等位基因携带者对GTN的反应显著延迟。在^*1/^*1和^*1/^*2，GTN扩张动脉的速度比ISDN快，但在^*2/^*2，GTN扩张动脉的速度不快。

To examine whether polymorphisms at codon 487 of aldehyde dehydrogenase 2 (ALDH2) influence nitroglycerin (GTN)-induced vasodilation, and whether GTN or isosorbide dinitrate (ISDN) is more effective in each genotype, we performed a crossover trial using sublingual spray of GTN and ISDN. Maximal artery diameter increase in response to GTN or ISDN did not differ among genotypes. However, the time required for dilation was longer in the ^*1/^*2 and ^*2/^*2 genotypes than ^*1/^*1. In contrast, ISDN-induced dilation did not differ among genotypes. The time required for GTN dilation was shorter than that for ISDN dilation among ^*1 allele carriers, whereas GTN and ISDN dilation did not differ among participants carrying ^*2/^*2. These results suggested that the response to GTN was significantly delayed in ^*2 allele carriers. GTN dilated the artery more quickly than ISDN in ^*1/^*1 and ^*1/^*2, but not in ^*2/^*2.