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The G(516)T CYP2B6 Germline Polymorphism Affects the Risk of Acute Myeloid Leukemia and Is Associated with Specific Chromosomal Abnormalities

The etiology of acute myeloid leukemia (AML) underlies the influence of genetic variants in candidate genes. The CYP2B6 enzyme detoxifies many genotoxic xenobiotics, protecting cells from oxidative damage. The CYP2B6 gene is subjected to a single-nucleotide polymorphism (G(516)T) with heterozygotes...

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Autores principales: Daraki, Aggeliki, Zachaki, Sophia, Koromila, Theodora, Diamantopoulou, Paraskevi, Pantelias, Gabriel E., Sambani, Constantina, Aleporou, Vasiliki, Kollia, Panagoula, Manola, Kalliopi N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3933334/
https://www.ncbi.nlm.nih.gov/pubmed/24586425
http://dx.doi.org/10.1371/journal.pone.0088879
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author Daraki, Aggeliki
Zachaki, Sophia
Koromila, Theodora
Diamantopoulou, Paraskevi
Pantelias, Gabriel E.
Sambani, Constantina
Aleporou, Vasiliki
Kollia, Panagoula
Manola, Kalliopi N.
author_facet Daraki, Aggeliki
Zachaki, Sophia
Koromila, Theodora
Diamantopoulou, Paraskevi
Pantelias, Gabriel E.
Sambani, Constantina
Aleporou, Vasiliki
Kollia, Panagoula
Manola, Kalliopi N.
author_sort Daraki, Aggeliki
collection PubMed
description The etiology of acute myeloid leukemia (AML) underlies the influence of genetic variants in candidate genes. The CYP2B6 enzyme detoxifies many genotoxic xenobiotics, protecting cells from oxidative damage. The CYP2B6 gene is subjected to a single-nucleotide polymorphism (G(516)T) with heterozygotes (GT) and homozygotes (TT) presenting decreased enzymatic activity. This case-control study aimed to investigate the association of CYP2B6 G(516)T polymorphism with the susceptibility of AML and its cytogenetic and clinical characteristics. Genotyping was performed on 619 AML patients and 430 healthy individuals using RCR-RFLP and a novel LightSNip assay. The major finding was a statistically higher frequency of the variant genotypes (GT and TT) in patients compared to the controls (GT:38.8% vs 29.8% and TT:9.3% vs 5.3% respectively) (p<0.001). More specifically, a significantly higher frequency of GT+TT genotypes in de novo AML patients (46.6%) and an immensely high frequency of TT in secondary AML (s-AML) (20.5%) were observed. The statistical analysis showed that the variant T allele was approximately 1.5-fold and 2.4-fold higher in de novo and s-AML respectively than controls. Concerning FAB subtypes, the T allele presented an almost 2-fold increased in AML-M2. Interestingly, a higher incidence of the TT genotype was observed in patients with abnormal karyotypes. In particular, positive correlations of the mutant allele were found in patients carrying specific chromosomal aberrations [-7/del(7q), -5/del(5q), +8, +21 or t(8;21)], complex or monosomal karyotypes. Finally, a strikingly higher frequency of TT genotype was also observed in patients stratified to the poor risk group. In conclusion, our results provide evidence for the involvement of the CYP2B6 polymorphism in AML susceptibility and suggest a possible role of the CYP2B6 genetic background on the development of specific chromosomal aberrations.
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spelling pubmed-39333342014-02-25 The G(516)T CYP2B6 Germline Polymorphism Affects the Risk of Acute Myeloid Leukemia and Is Associated with Specific Chromosomal Abnormalities Daraki, Aggeliki Zachaki, Sophia Koromila, Theodora Diamantopoulou, Paraskevi Pantelias, Gabriel E. Sambani, Constantina Aleporou, Vasiliki Kollia, Panagoula Manola, Kalliopi N. PLoS One Research Article The etiology of acute myeloid leukemia (AML) underlies the influence of genetic variants in candidate genes. The CYP2B6 enzyme detoxifies many genotoxic xenobiotics, protecting cells from oxidative damage. The CYP2B6 gene is subjected to a single-nucleotide polymorphism (G(516)T) with heterozygotes (GT) and homozygotes (TT) presenting decreased enzymatic activity. This case-control study aimed to investigate the association of CYP2B6 G(516)T polymorphism with the susceptibility of AML and its cytogenetic and clinical characteristics. Genotyping was performed on 619 AML patients and 430 healthy individuals using RCR-RFLP and a novel LightSNip assay. The major finding was a statistically higher frequency of the variant genotypes (GT and TT) in patients compared to the controls (GT:38.8% vs 29.8% and TT:9.3% vs 5.3% respectively) (p<0.001). More specifically, a significantly higher frequency of GT+TT genotypes in de novo AML patients (46.6%) and an immensely high frequency of TT in secondary AML (s-AML) (20.5%) were observed. The statistical analysis showed that the variant T allele was approximately 1.5-fold and 2.4-fold higher in de novo and s-AML respectively than controls. Concerning FAB subtypes, the T allele presented an almost 2-fold increased in AML-M2. Interestingly, a higher incidence of the TT genotype was observed in patients with abnormal karyotypes. In particular, positive correlations of the mutant allele were found in patients carrying specific chromosomal aberrations [-7/del(7q), -5/del(5q), +8, +21 or t(8;21)], complex or monosomal karyotypes. Finally, a strikingly higher frequency of TT genotype was also observed in patients stratified to the poor risk group. In conclusion, our results provide evidence for the involvement of the CYP2B6 polymorphism in AML susceptibility and suggest a possible role of the CYP2B6 genetic background on the development of specific chromosomal aberrations. Public Library of Science 2014-02-24 /pmc/articles/PMC3933334/ /pubmed/24586425 http://dx.doi.org/10.1371/journal.pone.0088879 Text en © 2014 Daraki et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Daraki, Aggeliki
Zachaki, Sophia
Koromila, Theodora
Diamantopoulou, Paraskevi
Pantelias, Gabriel E.
Sambani, Constantina
Aleporou, Vasiliki
Kollia, Panagoula
Manola, Kalliopi N.
The G(516)T CYP2B6 Germline Polymorphism Affects the Risk of Acute Myeloid Leukemia and Is Associated with Specific Chromosomal Abnormalities
title The G(516)T CYP2B6 Germline Polymorphism Affects the Risk of Acute Myeloid Leukemia and Is Associated with Specific Chromosomal Abnormalities
title_full The G(516)T CYP2B6 Germline Polymorphism Affects the Risk of Acute Myeloid Leukemia and Is Associated with Specific Chromosomal Abnormalities
title_fullStr The G(516)T CYP2B6 Germline Polymorphism Affects the Risk of Acute Myeloid Leukemia and Is Associated with Specific Chromosomal Abnormalities
title_full_unstemmed The G(516)T CYP2B6 Germline Polymorphism Affects the Risk of Acute Myeloid Leukemia and Is Associated with Specific Chromosomal Abnormalities
title_short The G(516)T CYP2B6 Germline Polymorphism Affects the Risk of Acute Myeloid Leukemia and Is Associated with Specific Chromosomal Abnormalities
title_sort g(516)t cyp2b6 germline polymorphism affects the risk of acute myeloid leukemia and is associated with specific chromosomal abnormalities
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3933334/
https://www.ncbi.nlm.nih.gov/pubmed/24586425
http://dx.doi.org/10.1371/journal.pone.0088879
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