Investigation of cytochrome p450 CYP1A2, CYP2D6, CYP2E1 and CYP3A4 gene expressions and polymorphisms in alcohol withdrawal (eng)

Abstract

INTRODUCTION[|]This study was designed to investigate the changes in expression levels of CYP1A2, CYP2D6, CYP2E1 and CYP3A4 genes in patients treated for alcohol dependence and a control group. The frequency of selected polymorphisms of these genes that might be a risk factor for alcohol-dependence and may affect the treatment success is also investigated. [¤]METHODS[|]Blood samples were collected in the beginning and at end of treatment from inpatients taking alcohol dependence treatment and from the control group. DNA and RNA isolation were performed. Gene expression was quantified by quantitative PCR (qPCR) and RFLP technique was used for polymorphism studies. [¤]RESULTS[|]No significant difference in the expression levels of studied genes in the patients before and after the treatment and between the control group was detected. However, a significant difference between the CYP1A2*F allele frequency in control and patient groups was observed. For CYP2D6*4 polymorphism, heterozygous genotypes have been detected in both patients and controls, whereas no CYP2D6*4/*4 was detected in either groups, indicating expression of a functional mRNA without reducing enzyme activity. No significant difference was found between the patient and control groups in the CYP2E1 c1/c2 polymorphism. CYP3A4*V polymorphism was not detected in either groups. [¤]DISCUSSION AND CONCLUSION[|]No difference in expression levels of studied genes in patients before and after treatment and in the control group was detected. A significant difference in the frequency of CYP1A2*1F c.734C>A polymorphism was detected between patient and control groups indicating a possible role of this allele as a risk factor for alcohol dependence.[¤]

Keywords

• alcohol
• addiction
• cyp
• gene expression
• polymorphism.