The Impact of Genetic Polymorphisms of Cytochrome P450 (CYP1A1&2D6) Gene in the Incidence of Acute Myeloid Leukaemia
Nada Abdalfatah Diab, Abozer Y. Elderdery, Jeremy Mills, Dawelbiet A. Yahia, Alsadig Gassoum, Sawsan Ahmed al-Deaf, Ashraf Abdelfatah Deyab, Entesar M Tebien, Hadeil M.E. Idris, Hiba B Khalil
1221
ABSTRACTBackground: A combination of risk factors effecting of genetic susceptibility and environmental exposure may explain the multi-step process of carcinogenesis/leukemogenesis of acute myeloid leukemia (AML).Aim: To evaluate the role of genetic polymorphisms of human cytochrome P450, namely CYP1A1 & CYP2D6 enzymes, involved in the transformation of chemical and cellular metabolism of drugs and carcinogenic agents as risk factors for AML Sudanese patients.Methods: A case control study was conducted between June 2016and June 2018 at the Radiation and Isotope Center Khartoum (RIKA), Sudan. A total of 265 blood specimens (200AML patients and 65 controls) were investigated for allele frequency and genotypes of CYP1A1*2C and CYP2D6*4. The DNA was extracted from all blood specimens, using Qiagen DNA extraction kit. Standard polymerase chain reaction and Restriction fragment length polymorphism analysis (PCR -RFLP) methods were used for genotyping.Results: Although no significant variations were evident for CYP1A1 AG genotype, the GG genotype showed significant differences. We also found no difference in frequencies of alleles A and G of gene CYP1A1 between patients. While, there is evidence of increased frequency when compared with control G allele. The genotype of the CYP2D6*4 allele revealed no significant differences between IM (heterozygous) and the mutant homozygous (PM) genotype. The PM allele for the CYP 2D6 gene was high in both patients and controls.Conclusions: Our findings illustrate that the genetic polymorphisms for xenobiotic metabolizing enzymes CYP1A1 heterozygous AG reveal no significant association with AML, where homozygous GG shows a protective effect. CYP2D6 suggests no association with the risk of AML for both heterozygous IM and the mutant homozygous PM.Key words: Cytochrome P450, CYP1A1, CYP 2D6 & AML
Background: A combination of risk factors effecting of genetic susceptibility and environmental exposure may explain the multi-step process of carcinogenesis/leukemogenesis of acute myeloid leukemia (AML).
Aim: To evaluate the role of genetic polymorphisms of human cytochrome P450, namely CYP1A1 & CYP2D6 enzymes, involved in the transformation of chemical and cellular metabolism of drugs and carcinogenic agents as risk factors for AML Sudanese patients.
Methods: A case control study was conducted between June 2016and June 2018 at the Radiation and Isotope Center Khartoum (RIKA), Sudan. A total of 265 blood specimens (200AML patients and 65 controls) were investigated for allele frequency and genotypes of CYP1A1*2C and CYP2D6*4. The DNA was extracted from all blood specimens, using Qiagen DNA extraction kit. Standard polymerase chain reaction and Restriction fragment length polymorphism analysis (PCR -RFLP) methods were used for genotyping.
Results: Although no significant variations were evident for CYP1A1 AG genotype, the GG genotype showed significant differences. We also found no difference in frequencies of alleles A and G of gene CYP1A1 between patients. While, there is evidence of increased frequency when compared with control G allele. The genotype of the CYP2D6*4 allele revealed no significant differences between IM (heterozygous) and the mutant homozygous (PM) genotype. The PM allele for the CYP 2D6 gene was high in both patients and controls.
Conclusions: Our findings illustrate that the genetic polymorphisms for xenobiotic metabolizing enzymes CYP1A1 heterozygous AG reveal no significant association with AML, where homozygous GG shows a protective effect. CYP2D6 suggests no association with the risk of AML for both heterozygous IM and the mutant homozygous PM.
Key words: Cytochrome P450, CYP1A1, CYP 2D6 & AML