Cytochrome P4502E1 (CYP2E1) gene shows genetic polymorphisms that vary markedly in frequency among different ethnic and racial groups. We studied the genotype distributions and allele frequencies of three CYP2E1 polymorphisms: CYP2E1*5B (RsaI/PstI RFLP, C-1053T/G-1293C SNP, rs2031920 /rs3813867), CYP2E1*6 (DraI RFLP, T7632A SNP, rs6413432), and CYP2E1*7B (DdeI RFLP, G-71T SNP, rs6413420) by PCR/RFLP technique in a sample of 206 healthy subjects representing Turkish population. CYP2E1*5B polymorphism analysis yielded the genotype distribution as 96.12% for *1A/*1A (c1/c1), and 3.88% for *1A/*5B (c1/c2). The genotype frequencies for CYP2E1*6 polymorphism were found as 83.98% for *1A/*1A (T/T), 15.53% for *1A/*6 (T/A) and 0.49% for *6/*6 (A/A). For CYP2E1*7B (G-71T) polymorphism, the genotype frequencies were determined to be 86.89% for *1A/*1A (G/G), 12.62% for *1A/*7B (G/T) and 0.49% for *7B/*7B (T/T). Accordingly, the allele frequencies for *5B, *6 and *7B were 1.94, 8.25, and 6.80%, respectively. The genotype distributions of CYP2E1*5B and *6 in Turkish population were similar to those in other Caucasian populations, while differed significantly from East Asian populations. Recently, a novel and functionally important CYP2E1*7B polymorphism was identified in the promoter region. There have been few studies and limited data on CYP2E1*7B polymorphism frequency in the world and, so far, no information has been available for Turkish population. The genotype frequencies of CYP2E1*7B in Turkish population were found to be similar to those of other Caucasian populations. Population studies like this could be useful in assessing the susceptibility of different populations to chemical-induced diseases, including several types of cancer.

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Background/Aims: The molecular etiology of childhood acute lymphoblastic leukemia (ALL) is likely to involve interactions between environmental factors and genetic make up. Understanding these interactions between various predisposing genes for the risk of developing childhood leukemia is of considerable importance. CYP2E1 is a susceptible gene in this respect, especially for its capacity to bioactivate many procarcinogens including benzene and N-nitrosodimethylamine. The CYP2E1 gene possesses several polymorphisms in humans, and among them, CYP2E1*5B and *6 have been shown to be associated with increased risks of several chemical-induced diseases. There are limited and contradictory data on the association between the CYP2E1*5B variant allele and childhood ALL, and none on such associations of CYP2E1*6 and*7B variant alleles. The aim of this study was to investigate the possible association of CYP2E1*5B, *6 and *7B alleles, alone or in combination, with the risk of incidence of childhood ALL in a Turkish population. Methods: The genotypes for both polymorphisms were determined by polymerase chain reaction/restriction fragment length polymorphism techniques on 207 healthy controls and 168 patients. Results: Neither locus was associated with the occurrence of childhood ALL. On the other hand, when both CYP2E1*5B and *6 alleles were considered together, the risk of childhood ALL increased significantly (2.9-fold; OR = 2.9, 95% CI 1.0–8.5; p < 0.05). Moreover, the presence of at least 2 variant alleles of any combination increased the risk significantly 3.9 times, suggesting a combined effect (OR = 3.9, 95% CI 1.4–11.0). Conclusion: Individuals carrying combinations of CYP2E1*5B, *6 and *7B variants together are likely associated with the risk of developing childhood ALL.

6-Mercaptopurine (6MP) is an essential anticancer drug used in the treatment of childhood acute lymphoblastic leukemia (ALL). Thiopurine methyltransferase (TPMT) polymorphisms are the major determinants of interindividual differences in the severe toxicity or efficacy of 6MP. Four variant alleles, TPMT*2, TPMT*3A, TPMT*3B, and TPMT*3C, are responsible over the 80% of low or undetectable enzyme activity. The frequencies of these variants were investigated among 106 children with ALL in Turkish population. TPMT*3A and TPMT*3C were the only deficiency alleles detected in Turkish population with an allele frequency of 0.9% for both. While *3C allele frequency in Turkish population was found to be very similar to Asian and other Caucasian populations, *3A allele frequency was significantly (P < 0.05) lower. So far, studies showed that the genetic polymorphisms of other drug metabolizing enzymes like CYP2E1, CYP1A1, GSTM1/ T1 in Turkish population were similar to Caucasian populations. However, we found that the distribution of TPMT polymorphisms in Turkish population was significantly lower than those in other Caucasians like British, French, and Italian whereas the distributions of TPMT variants were found to be very similar to Kazak population which is also Caucasian in ethnic origin. In this study, the clinical histories of the patients in the sample population were also examined, retrospectively. The patients with heterozygous or homozygous mutant genotypes had developed severe neutropenia and infection during 6MP therapy. The study provides the first data on the frequency of common TPMT variants in the Turkish population, based on analysis of pediatric patients with ALL.