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.
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 language | English |
|---|---|
| Pages (from-to) | 899-904 |
| Number of pages | 6 |
| Journal | Pakistani Journal of Medical and Health Sciences |
| Volume | 14 |
| Issue number | 3 |
| Publication status | Published - 1 Jul 2020 |
Keywords
- Cytochrome P450
- CYP1A1
- CYP 2D6 & AML