Detection of Polymorphism in Cytochrome P450 (CYP3A5) and Sulfertranseferase (SULT1A1) Genes in Patients with Leukemia in Sudan

Abstract

This is a case - control study done to investigate genetic differences among Sudanese patients with leukemia and aimed to evaluate the impact of the CYP3A5 and SULT1A1 metabolizing enzyme gene polymorphisms on the risk of leukemia. The analysis was conducted on 100 patients with leukemia referred to Radiation and Isotopes Centre Khartoum (RICK), and 100 healthy individuals as control group. patients were fully informed about the aims of the study, besides approved written consent. DNA extracted from EDTA blood samples and PCR-RFLP performed for each patient and control subject. two primer pairs were designed according to published sequence data for, intron 3 in CYP3A5, exon 7 in SULT1A1.The different genotypes were scored for each locus and data were analyzed using computer software SPSS (versoin17). Distribution of leukemia among patients revealed that leukemia According to gender occurrence of leukemia in males was 62 (62%) with frequencies CML 16 (64%), CLL 14(54%), AML 10 (48%) and ALL 22(79%). The frequency of leukemia among female patients was 38 (38%) distributed as CML 9 (36%), CLL 12 (46%), AML 11 (52%) and ALL 6 (21%). The mutant CYP3A5*3/*3 genotype was more frequent among study group (P value = 0.001) in contrast sulotransferase 1A1 mutant SULT *2/*2 genotype shows insignificant value (P value = 0.446), in relation to type of leukemia CYP3A5*3/*3 frequencies in CML was 11 (42.3%), CLL 8 (30.8%) AML 3 (11.5%) and ALL 4 (15.4%). While the mutant SULT *2/*2 frequency was 5 (45.46%) in CML and 2 (18.18%) in CLL, AML and ALL respectively. In conclusion, CYP3A5 variants exhibit significant risk associated with leukemia particularly mutant type CYP3A5*3/*3 allele. Gender is an important modulator of the risk and may explain certain aspects related to male / female incidence of leukemia.