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Ali GT, Al-Azhary NM, Mokhtar DA. Frequency and prognostic significant of CYP3A4-A-290G polymorphism in acute myeloid leukemia. J Adv Res. 2013;5(6):657-61doi: 10.1016/j.jare.2013.10.002.
Ali, G. T., Al-Azhary, N. M., & Mokhtar, D. A. (2014). Frequency and prognostic significant of CYP3A4-A-290G polymorphism in acute myeloid leukemia. Journal of advanced research, 5(6), 657-61. https://doi.org/10.1016/j.jare.2013.10.002
Ali, Gamal T, et al. "Frequency and prognostic significant of CYP3A4-A-290G polymorphism in acute myeloid leukemia." Journal of advanced research vol. 5,6 (2014): 657-61. doi: https://doi.org/10.1016/j.jare.2013.10.002
Ali GT, Al-Azhary NM, Mokhtar DA. Frequency and prognostic significant of CYP3A4-A-290G polymorphism in acute myeloid leukemia. J Adv Res. 2014 Nov;5(6):657-61. doi: 10.1016/j.jare.2013.10.002. Epub 2013 Oct 30. PMID: 25685534; PMCID: PMC4293909.
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J Adv Res. 2014 Nov;5(6):657-61. doi: 10.1016/j.jare.2013.10.002. Epub 2013 Oct 30.

Frequency and prognostic significant of CYP3A4-A-290G polymorphism in acute myeloid leukemia.

Journal of advanced research

Gamal T Ali, Nevin M Al-Azhary, Doha A Mokhtar

Affiliations

  1. Clinical Pathology Department, National Cancer Institute, Cairo University, Cairo, Egypt.
  2. Clinical Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.

PMID: 25685534 PMCID: PMC4293909 DOI: 10.1016/j.jare.2013.10.002

Abstract

Cytochrome P450 3A4 (CYP3A4) is the most plentiful cytochrome P450 in adult human liver and small intestine and is responsible for detoxification of more than 50% of drugs in addition to the metabolic deactivation and metabolism of many carcinogens. Polymorphism of CYP3A4-A-290G considered the only allele that appears to stimulate CYP3A4 expression and has been associated with a number of clinical phenotypes, including prostate cancer, breast cancer, leukemia and the early onset of puberty. In this study, we analyzed the presence of CYP3A4-A-290G polymorphism in 77 newly diagnosed AML cases and 72 healthy control using PCR/RFLP aiming to show CYP3A4-A-290G polymorphism pattern in acute myeloid leukemia patients, and its role in disease severity and progression. A highly statistically significant difference was found between the control and AML groups as regards the heterozygous genotype (p-value = 0.002) and increases the risk of AML 11.4-fold. Also there was a highly significant difference between the control and AML patients regarding variant allele (G in AG and GG genotypes) (p-value 0.001) and increases the risk of AML 19-fold. No statistically significant association found between the CYP3A4-A-290G polymorphism and different clinical or laboratory parameters as well as an initial response to treatment, overall survival and the disease free survival. We concluded that CYP3A4-A-290G polymorphism is a genotypic factor that increases the CYP3A4 enzymatic activity and increases the risk of AML by 18.9-fold.

Keywords: 290G; AML; CYP3A4-A; PCR/RFLP; Prognosis

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