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The Impact of Genetic Polymorphisms of Cytochrome P450 (CYP1A1&2D6) Gene in the Incidence of Acute Myeloid Leukaemia
Author(s):
1. NADA ABDALFATAH DIAB: Faculty of Medical Laboratory Sciences, Al Neelain University, Sudan; Faculty of Medical Laboratory Sciences, University Of Khartoum, Sudan.
2. ABOZER Y. ELDERDERY: Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Saudi Arabia; Faculty of Medical Laboratory Sciences, University of El Imam El Mahdi, Sudan
3. JEREMY MILLS: School of Pharmacy and Biomedical Sciences, University of Portsmouth, UK
4. DAWELBIET A. YAHIA: Faculty of Medicine, University of El Imam El Mahdi, Sudan
5. AlSADIG GASSOUM: National Center for Neurological Sciences (NCNS), Khatoum, Sudan
6. SAWSAN AHMED AL-DEAF: National Center for Neurological Sciences (NCNS),,Sudan
7. ASHRAF ABDELFATAH DEYAB: College of Medicine, Majmaah University,KSA,
8. ENTESAR M TEBIEN: Faculty of Medical Laboratory Sciences, Al Neelain University, Sudan ;Faculty of Applied Medical Sciences, Clinical Laboratory Sciences, Shaqra University, Saudi Arabia
9. HADEIL M.E. IDRIS: Faculty of Medical Laboratory Sciences, Al Neelain University, Sudan ;Faculty of Applied Medical Sciences, Clinical Laboratory Sciences, Shaqra University, Saudi Arabia
10. HIBA B KHALIL: Faculty of Medical Laboratory Sciences, Al Neelain University,,Sudan
Abstract:
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). Objectives: The study objective is 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/design: 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.
Page(s): 899-904
DOI: DOI not available
Published: Journal: Pakistan Journal of Medical and Health Sciences, Volume: 14, Issue: 3, Year: 2020
Keywords:
CYP1A1 , cytochrome P450 , CYP 2D6 and AML
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