ABSTRACT
CYP enzymes are involved in the metabolism of various endogenous and exogenous chemicals, including steroids, bile acids, fatty acids, eicosanoids, xenobiotics, environmental pollutants, and carcinogens (Nebert and Dalton 2006; Nebert and Russell 2002; Nebert et al. 2013). Human CYPs are important in physiology, drug metabolism, and pathogenesis of certain diseases, and thus there is a strong need to explore the genetic variations and regulatory mechanisms of these enzymes. Mutations in CYP genes leading to deficiency in the enzymes result in a wide spectrum of human diseases such as glaucoma (CYP1B1), elevated cholesterol (CYP7A1), congenital adrenal hyperplasia, congenital hypoaldosteronism (CYP11B2), essential hypertension (CYP4A11), Bietti’s crystalline corneoretinal dystrophy (CYP4V2), lamellar ichthyosis (CYP4F22), and cancers (Nebert et al. 2013). Members of families CYP1, CYP2, and CYP3, especially CYP1A2, 2B6, 2C9, 2C19, 2D6, and 3A4 in liver, metabolize approximately 95% of clinical drugs (Hodgson and Rose 2007; Nebert et al. 2013), which are also active in the formation of carcinogens from procarcinogens (Ghoshal et al. 2014; Go et al. 2015; Panigrahy et al. 2010; Raunio and Rahnasto-Rilla 2012; Rodriguez and Potter 2013; Xiang et al. 2015; Xu et al. 2013). Many CYPs are linked to cancer growth, development, and metastasis via multiple mechanisms (Choong et al. 2015; Go et al. 2015; Ye et al. 2015). The CYP4 family members are involved in the disposition of fatty acids and eicosanoids (Hsu et al. 2007; Simpson 1997), whereas members of CYP11, 17, 19, and 21 families are steroidogenic enzymes in tissues such as adrenal cortex, ovaries, and testes (Niwa et al. 2009; Snider et al. 2010). A number of clinical studies have shown that polymorphisms in CYP2D6 and CYP2C19 are linked to altered response or occurrence of adverse drug reactions (ADRs) of various drugs used in the treatment of cancer, psychiatric disorders, and cardiovascular diseases (Zhou 2009a,b). In addition to genetic polymorphisms within CYP genes, regulatory mechanisms at transcriptional, translational, posttranslational, and epigenetic levels also contribute to the large variability in CYP expression and activities observed across ethnic groups and individuals (Polimanti et al. 2012; Sinz et al. 2008; Tralau and Luch 2013).
