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Genetic polymorphisms associated with increased risk of developing chronic myelogenous leukemia
Little is known about inherited factors associated with the risk of developing chronic myelogenous leukemia (CML). We used a dedicated DNA chip containing 16 561 single nucleotide polymorphisms (SNPs) covering 1 916 candidate genes to analyze 437 CML patients and 1 144 healthy control individuals. S...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4742176/ https://www.ncbi.nlm.nih.gov/pubmed/26474455 |
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author | Bruzzoni-Giovanelli, Heriberto González, Juan R. Sigaux, François Villoutreix, Bruno O. Cayuela, Jean Michel Guilhot, Joëlle Preudhomme, Claude Guilhot, François Poyet, Jean-Luc Rousselot, Philippe |
author_facet | Bruzzoni-Giovanelli, Heriberto González, Juan R. Sigaux, François Villoutreix, Bruno O. Cayuela, Jean Michel Guilhot, Joëlle Preudhomme, Claude Guilhot, François Poyet, Jean-Luc Rousselot, Philippe |
author_sort | Bruzzoni-Giovanelli, Heriberto |
collection | PubMed |
description | Little is known about inherited factors associated with the risk of developing chronic myelogenous leukemia (CML). We used a dedicated DNA chip containing 16 561 single nucleotide polymorphisms (SNPs) covering 1 916 candidate genes to analyze 437 CML patients and 1 144 healthy control individuals. Single SNP association analysis identified 139 SNPs that passed multiple comparisons (1% false discovery rate). The HDAC9, AVEN, SEMA3C, IKBKB, GSTA3, RIPK1 and FGF2 genes were each represented by three SNPs, the PSM family by four SNPs and the SLC15A1 gene by six. Haplotype analysis showed that certain combinations of rare alleles of these genes increased the risk of developing CML by more than two or three-fold. A classification tree model identified five SNPs belonging to the genes PSMB10, TNFRSF10D, PSMB2, PPARD and CYP26B1, which were associated with CML predisposition. A CML-risk-allele score was created using these five SNPs. This score was accurate for discriminating CML status (AUC: 0.61, 95%CI: 0.58–0.64). Interestingly, the score was associated with age at diagnosis and the average number of risk alleles was significantly higher in younger patients. The risk-allele score showed the same distribution in the general population (HapMap CEU samples) as in our control individuals and was associated with differential gene expression patterns of two genes (VAPA and TDRKH). In conclusion, we describe haplotypes and a genetic score that are significantly associated with a predisposition to develop CML. The SNPs identified will also serve to drive fundamental research on the putative role of these genes in CML development. |
format | Online Article Text |
id | pubmed-4742176 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-47421762016-04-04 Genetic polymorphisms associated with increased risk of developing chronic myelogenous leukemia Bruzzoni-Giovanelli, Heriberto González, Juan R. Sigaux, François Villoutreix, Bruno O. Cayuela, Jean Michel Guilhot, Joëlle Preudhomme, Claude Guilhot, François Poyet, Jean-Luc Rousselot, Philippe Oncotarget Research Paper Little is known about inherited factors associated with the risk of developing chronic myelogenous leukemia (CML). We used a dedicated DNA chip containing 16 561 single nucleotide polymorphisms (SNPs) covering 1 916 candidate genes to analyze 437 CML patients and 1 144 healthy control individuals. Single SNP association analysis identified 139 SNPs that passed multiple comparisons (1% false discovery rate). The HDAC9, AVEN, SEMA3C, IKBKB, GSTA3, RIPK1 and FGF2 genes were each represented by three SNPs, the PSM family by four SNPs and the SLC15A1 gene by six. Haplotype analysis showed that certain combinations of rare alleles of these genes increased the risk of developing CML by more than two or three-fold. A classification tree model identified five SNPs belonging to the genes PSMB10, TNFRSF10D, PSMB2, PPARD and CYP26B1, which were associated with CML predisposition. A CML-risk-allele score was created using these five SNPs. This score was accurate for discriminating CML status (AUC: 0.61, 95%CI: 0.58–0.64). Interestingly, the score was associated with age at diagnosis and the average number of risk alleles was significantly higher in younger patients. The risk-allele score showed the same distribution in the general population (HapMap CEU samples) as in our control individuals and was associated with differential gene expression patterns of two genes (VAPA and TDRKH). In conclusion, we describe haplotypes and a genetic score that are significantly associated with a predisposition to develop CML. The SNPs identified will also serve to drive fundamental research on the putative role of these genes in CML development. Impact Journals LLC 2015-10-12 /pmc/articles/PMC4742176/ /pubmed/26474455 Text en Copyright: © 2015 Bruzzoni-Giovanelli et al. http://creativecommons.org/licenses/by/2.5/ 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 credited. |
spellingShingle | Research Paper Bruzzoni-Giovanelli, Heriberto González, Juan R. Sigaux, François Villoutreix, Bruno O. Cayuela, Jean Michel Guilhot, Joëlle Preudhomme, Claude Guilhot, François Poyet, Jean-Luc Rousselot, Philippe Genetic polymorphisms associated with increased risk of developing chronic myelogenous leukemia |
title | Genetic polymorphisms associated with increased risk of developing chronic myelogenous leukemia |
title_full | Genetic polymorphisms associated with increased risk of developing chronic myelogenous leukemia |
title_fullStr | Genetic polymorphisms associated with increased risk of developing chronic myelogenous leukemia |
title_full_unstemmed | Genetic polymorphisms associated with increased risk of developing chronic myelogenous leukemia |
title_short | Genetic polymorphisms associated with increased risk of developing chronic myelogenous leukemia |
title_sort | genetic polymorphisms associated with increased risk of developing chronic myelogenous leukemia |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4742176/ https://www.ncbi.nlm.nih.gov/pubmed/26474455 |
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