The G⁵¹⁶T 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 (G⁵¹⁶T) with heterozygotes (G...

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Autores principales: Aggeliki Daraki, Sophia Zachaki, Theodora Koromila, Paraskevi Diamantopoulou, Gabriel E Pantelias, Constantina Sambani, Vasiliki Aleporou, Panagoula Kollia, Kalliopi N Manola
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Publicado: Public Library of Science (PLoS) 2014
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spelling oai:doaj.org-article:7697b0012bf848089a55614e42c56fa22021-11-18T08:31:24ZThe G⁵¹⁶T CYP2B6 germline polymorphism affects the risk of acute myeloid leukemia and is associated with specific chromosomal abnormalities.1932-620310.1371/journal.pone.0088879https://doaj.org/article/7697b0012bf848089a55614e42c56fa22014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24586425/?tool=EBIhttps://doaj.org/toc/1932-6203The 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 (G⁵¹⁶T) with heterozygotes (GT) and homozygotes (TT) presenting decreased enzymatic activity. This case-control study aimed to investigate the association of CYP2B6 G⁵¹⁶T 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.Aggeliki DarakiSophia ZachakiTheodora KoromilaParaskevi DiamantopoulouGabriel E PanteliasConstantina SambaniVasiliki AleporouPanagoula KolliaKalliopi N ManolaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 2, p e88879 (2014)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Aggeliki Daraki
Sophia Zachaki
Theodora Koromila
Paraskevi Diamantopoulou
Gabriel E Pantelias
Constantina Sambani
Vasiliki Aleporou
Panagoula Kollia
Kalliopi N Manola
The G⁵¹⁶T CYP2B6 germline polymorphism affects the risk of acute myeloid leukemia and is associated with specific chromosomal abnormalities.
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 (G⁵¹⁶T) with heterozygotes (GT) and homozygotes (TT) presenting decreased enzymatic activity. This case-control study aimed to investigate the association of CYP2B6 G⁵¹⁶T 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.
format article
author Aggeliki Daraki
Sophia Zachaki
Theodora Koromila
Paraskevi Diamantopoulou
Gabriel E Pantelias
Constantina Sambani
Vasiliki Aleporou
Panagoula Kollia
Kalliopi N Manola
author_facet Aggeliki Daraki
Sophia Zachaki
Theodora Koromila
Paraskevi Diamantopoulou
Gabriel E Pantelias
Constantina Sambani
Vasiliki Aleporou
Panagoula Kollia
Kalliopi N Manola
author_sort Aggeliki Daraki
title The G⁵¹⁶T CYP2B6 germline polymorphism affects the risk of acute myeloid leukemia and is associated with specific chromosomal abnormalities.
title_short The G⁵¹⁶T CYP2B6 germline polymorphism affects the risk of acute myeloid leukemia and is associated with specific chromosomal abnormalities.
title_full The G⁵¹⁶T CYP2B6 germline polymorphism affects the risk of acute myeloid leukemia and is associated with specific chromosomal abnormalities.
title_fullStr The G⁵¹⁶T CYP2B6 germline polymorphism affects the risk of acute myeloid leukemia and is associated with specific chromosomal abnormalities.
title_full_unstemmed The G⁵¹⁶T CYP2B6 germline polymorphism affects the risk of acute myeloid leukemia and is associated with specific chromosomal abnormalities.
title_sort g⁵¹⁶t cyp2b6 germline polymorphism affects the risk of acute myeloid leukemia and is associated with specific chromosomal abnormalities.
publisher Public Library of Science (PLoS)
publishDate 2014
url https://doaj.org/article/7697b0012bf848089a55614e42c56fa2
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