Distribution of xenobiotic metabolising enzyme genotypes in different Tunisian populations.

BACKGROUND: The N-acetyltransferase 2 (NAT2) and glutathione transferase enzymes play a crucial role in the metabolism of xenobiotics. Genetic polymorphisms affecting these enzymes can modify their activities with an effect on individual susceptibility for different pathologies. These metabolic phenotypes occur with varying prevalence in different populations. AIM: This study sought to analyse the prevalence of important allelic variants of NAT2, GSTM1 and GSTT1 in different Tunisian populations and compare them to other previously reported data. SUBJECTS AND METHODS: A total of 253 unrelated subjects from different Tunisian populations participated in this study. Subjects were examined with respect to the frequency of slow NAT2, GSTM1*0 and GSTT1*0 genotypes. RESULTS: The frequency of 'slow' NAT2, GSTM1*0 and GSTT1*0 genotypes in the Tunisian population were, respectively, estimated at 23.3%, 53.75% and 29.24%. The frequency of slow NAT2 and GSTM1*0 genotypes were significantly different between the North, Centre and South of Tunisia. However, this study doesn't report any significant differences in the genotype distribution between Cosmopolitan, Arab and Berber populations. CONCLUSIONS: In conclusion, these data indicate that the Tunisian population is highly heterogenic and, therefore, a strict definition of the populations involved in studies investigating the clinical effect of polymorphisms is required.

Influence of genetic polymorphisms of xenobiotic metabolizing enzymes on the risk of developing leukemia in a Tunisian population.

Leukemia is a type of cancer of the blood or bone marrow that is characterized by an abnormal increase of white blood cells. Leukemia is clinically and pathologically subdivided into a variety of large groups. The risk of developing leukemia may be influenced by polymorphisms of xenobiotic metabolizing enzymes. In this work, we conduct a case-control study to assess the impact of polymorphisms in GSTM1, GSTT1 and NAT2 genes on the risk of developing leukemia. Our data have shown that GSTM1*0 and GSTT1*0 were respectively associated with 2.05 and 4.36 increased risk for acute lymphoblastic leukemia (ALL). We have also shown that GSTM1*0 and GSTT1*0 act additively to increase the risk for ALL. Indeed, patients harbouring the "GSTM1*0/GSTT1*0" genotype were at 11.81-fold increased risk for developing ALL (P = 2 10(-5)). The risk for developing acute myeloid leukemia (AML) increases on patients with "rapid or intermediate NAT2 genotypes". Finally, the comparison of leukemia subgroups according to GSTM1, GSTT1 and NAT2 genotypes, suggests that leukemogenesis of different leukemia subgroups is very distinct. In conclusion, our findings suggest that leukemogenesis is associated with carcinogen metabolism and consequently related to environmental exposures.