The impact of genetic polymorphisms of cytochrome P450 (CYP1A1&2D6) gene in the incidence of acute myeloid leukaemia

N. A. Diab, A. Y. Elderdery, Jeremy Mills, D. A. Yahia, A. Gassoum, Sawsan Ahmed Al-Deaf, A. A. Deyab, E. M. Tebien, H. M. E. Idris, H. B. Khalil

Research output: Contribution to journalArticlepeer-review

Abstract

Background: A combination of risk factors effecting of genetic susceptibility and environmental exposure mayexplain 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 & CYP2D6enzymes, involved in the transformation of chemical and cellular metabolism of drugs and carcinogenic agents asrisk factors for AML Sudanese patients. 

Methods: A case control study was conducted between June 2016and June 2018 at the Radiation and IsotopeCenter Khartoum (RIKA), Sudan. A total of 265 blood specimens (200AML patients and 65 controls) wereinvestigated for allele frequency and genotypes of CYP1A1*2C and CYP2D6*4. The DNA was extracted from allblood specimens, using Qiagen DNA extraction kit. Standard polymerase chain reaction and Restriction fragmentlength polymorphism analysis (PCR -RFLP) methods were used for genotyping. 

Results: Although no significant variations were evident for CYP1A1 AG genotype, the GG genotype showedsignificant differences. We also found no difference in frequencies of alleles A and G of gene CYP1A1 betweenpatients. While, there is evidence of increased frequency when compared with control G allele. The genotype ofthe 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 enzymesCYP1A1 heterozygous AG reveal no significant association with AML, where homozygous GG shows a protectiveeffect. CYP2D6 suggests no association with the risk of AML for both heterozygous IM and the mutanthomozygous PM.
Original languageEnglish
Pages (from-to)1221-1226
Number of pages6
JournalPakistani Journal of Medical and Health Sciences
Volume14
Issue number3
Publication statusPublished - 1 Jul 2020

Keywords

  • Cytochrome P450
  • CYP1A1
  • CYP 2D6 & AML

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