Genetic polymorphisms of CYP genes in Serbian population

Cytochrome P450 (CYP) is a superfamily of more than 60 heme-containing, membrane bound, monoxygensase enzymes, responsible for much of the oxidative metabolism occurring in the body. Some of these enzymes, evolutionary older and predominantly located in mitochondria, are mainly involved in the synthesis and excretion of steroids. Other CYPs, located in the smooth endoplasmic reticulum, are responsible for the phase I metabolism of many foreign biological substances (xenobiotics), playing a critical role in response to dietary and environmental toxins, carcinogens and therapeutic drugs. According to the activity of a specific CYP enzyme, a person can be identified either as slow (SM), normal (NM), extensive (EM) or ultra metabolizer (UM). The activity of CYPs in the body (mostly in the liver) depends on various external and internal factors. Some of the CYPs are inducible and others are constitutively expressed. The levels of expression, and hence the activity, of both inducible and constitutive CYPs are largely influenced by genetic polymorphisms found in many CYP genes. Frequency distributions of variant alleles of CYP genes are racially and ethnically dependent. The association of various allelic variants and metabolizer status has been extensively studied. The proposed investigations will focus on identifying variant alleles of several clinically and/or toxicologically important CYP isoenzymes (CYP1A1/2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4/5) in Serbian population.