CYP2E1 VNTR polymorphisms and hepatocarcinoma: a gender-specific correlation

Cytochrome P450 (CYP2E1) is often associate to susceptibility to alcohol-related diseases and various cancers, because of its role in the metabolism of multiple environmental xenobiotics. In the 5’- flanking region of the human CYP2E1 gene there are restriction fragment length polymorphism which are involved in the transcriptional regulation of the CYP2E1 gene. Recently a tandem repeat polymorphism (VNTR) in the 5’-flanking region of CYP2E1 was found. Because cytochrome P450 2E1 catalyzes the metabolic activation of pro-carcinogen and cytotoxic compound, we value the genetic distribution of this tandem repeat polymorphism in a healthy population, and in patients with hepatocellular carcinoma living in same country, in order to found a correlation between CYP2E1 VNTR genotype and neoplasia. DNA was isolated from spit sample of 108 control subject and from the peripheral lymphocytes of 35 HCC patients. The 5’ flanking region of the CYP2E1 gene was amplified by polymerase chain reaction and examined for tandem repeat polymorphism using Nla IV restriction map. This study reports that only four of the ten possible genotype were found in all subjects. The modal genotype, found in both analyzed populations, is A2/A2. Interestingly, in a gender-based analysis of data this genotype was found more frequent in woman with disease that in control ones. These preliminary findings represent a first report of a gender-specific correlation between CYP2E1 VNTR polymorphism and hepatocarcinoma.