Gross Eric R, Zambelli Vanessa O, Small Bryce A, Ferreira Julio C B, Chen Che-Hong, Mochly-Rosen Daria
Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, School of Medicine, Stanford, California 94305.
Annu Rev Pharmacol Toxicol. 2015;55:107-27. doi: 10.1146/annurev-pharmtox-010814-124915. Epub 2014 Sep 29.
Asian Americans are one of the fastest-growing populations in the United States. A relatively large subset of this population carries a unique loss-of-function point mutation in aldehyde dehydrogenase 2 (ALDH2), ALDH22. Found in approximately 560 million people of East Asian descent, ALDH22 reduces enzymatic activity by approximately 60% to 80% in heterozygotes. Furthermore, this variant is associated with a higher risk for several diseases affecting many organ systems, including a particularly high incidence relative to the general population of esophageal cancer, myocardial infarction, and osteoporosis. In this review, we discuss the pathophysiology associated with the ALDH22 variant, describe why this variant needs to be considered when selecting drug treatments, and suggest a personalized medicine approach for Asian American carriers of this variant. We also discuss future clinical and translational perspectives regarding ALDH22 research.
亚裔美国人是美国增长最快的人群之一。该人群中相对较大的一部分携带醛脱氢酶2(ALDH2)的一种独特的功能丧失点突变,即ALDH22。在大约5.6亿东亚血统的人群中发现,杂合子中ALDH22会使酶活性降低约60%至80%。此外,这种变异与影响多个器官系统的多种疾病的较高风险相关,包括相对于普通人群而言,食管癌、心肌梗死和骨质疏松症的发病率特别高。在这篇综述中,我们讨论了与ALDH22变异相关的病理生理学,描述了在选择药物治疗时为何需要考虑这种变异,并为携带这种变异的亚裔美国人提出了一种个性化医疗方法。我们还讨论了关于ALDH22研究的未来临床和转化前景。