Investigation of CYP1B1 gene polymorphism in a Turkish population


Ada A. O. (Executive)

Project Supported by Higher Education Institutions, 2010 - 2013

  • Project Type: Project Supported by Higher Education Institutions
  • Begin Date: October 2010
  • End Date: October 2013

Project Abstract

The bioactivation of many carcinogenic compounds occur after oxidation with phase I enzymes which they undergo extensive metabolic activation by cytochrome P450 (CYP) enzyme superfamily. Thus changes in the expression of CYPs is an effective toxicological factor. One of the most important groups of metabolic enzymes which are responsible for the disposal of toxic substances is CYP superfamily. An important isozyme of this superfamily is CYP1B1 isozyme. CYP1B1 is a key enzyme involved in the formation of estrogen metabolites and activation of environmental carcinogens such as polycyclic aromatic hydrocarbons. The products formed after metabolic activation become substantially more toxic than the original compound. There are five different single nucleotide polymorphisms exist in the human CYP1B1 gene which cause changes in enzyme activity, namely Arg48Gly (CYP1B1*2), Ala119Ser (CYP1B1*2), Leu432Val (CYP1B1*3), Asn453Ser (CYP1B1*4) and Ala443Gly (CYP1B1*7).  Generally mutant CYP1B1 isozymes show higher activity when compared with the wild type. In individuals with high CYP1B1 activity, due to the formation of mutagenic and carcinogenic active intermediates of both endogenous substances and exogenous environmental chemicals, the risk of developing different types of cancer may also be higher. Polymorphic gene frequencies in several populations are reported to be different. In addition, there are differences within ethnic groups. In Turkey there exist very few studies on CYP1B1 polymorphisms and the incidence of these polymorphisms in Turkish population has not been clarified. Therefore, in this study the Arg48Gly (CYP1B1*2), Ala119Ser (CYP1B1*2), Leu432Val (CYP1B1*3), Asn453Ser (CYP1B1*4) and Ala443Gly (CYP1B1*7) polymorphisms were determined in 125 men and 125 women, a total of 250 volunteers. Results of this study provide information about the polymorphic distribution of CYP1B1 gene in Turkish population and give the possibility for comparison with other populations. Also the results can constitute basic data for determining the extent of the effect of these polymorphisms in various diseases and cancer.