Koukouritaki Sevasti B, Hines Ronald N
Medical College of Wisconsin, Department of Pediatrics, Clinical Pharmacology, Pharmacogenetics and Teratology Section, 8701 Watertown Plank Rd., Milwaukee, Wisconsin 53226, USA.
Pharmacogenomics. 2005 Dec;6(8):807-22. doi: 10.2217/14622416.6.8.807.
The flavin-containing monooxygenases (FMOs) metabolize a broad range of therapeutics. Consisting of five gene products in humans (FMO1-5), the different FMO family members exhibit pronounced tissue- and temporal-specific expression patterns. Substantial interindividual differences are also observed, and the inability to modulate with exogenous agents is consistent with an important role for genetic variation. Several rare FMO3 alleles causative for trimethylaminuria have been well characterized. However, the identification and characterization of functional FMO1-5 polymorphisms has been more recent. Although none of these polymorphisms has been associated with an adverse drug reaction, the continued broadening of our therapeutic armamentarium makes such an event likely in the future. Furthermore, at least one example has been reported for a direct association between FMO3 polymorphism and therapeutic efficacy. Thus, it is anticipated that knowledge regarding functionally-relevant FMO genetic variability will become increasingly important for making drug development and patient therapeutic choices.
含黄素单加氧酶（FMOs）可代谢多种治疗药物。人类的FMOs由五种基因产物（FMO1 - 5）组成，不同的FMO家族成员表现出明显的组织和时间特异性表达模式。个体间也存在显著差异，且无法通过外源性药物进行调节，这与基因变异的重要作用是一致的。几种导致三甲胺尿症的罕见FMO3等位基因已得到充分表征。然而，功能性FMO1 - 5多态性的鉴定和表征则是最近才开展的。尽管这些多态性均未与药物不良反应相关联，但随着我们治疗药物库的不断扩大，未来发生这种情况的可能性很大。此外，已有至少一个例子报道了FMO3多态性与治疗效果之间的直接关联。因此，预计有关功能相关FMO基因变异性的知识对于药物开发和患者治疗选择将变得越来越重要。
