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Functional polymorphisms of DNA repair genes in Latin America reinforces the heterogeneity of Myelodysplastic Syndrome

Nucleotide excision repair pathway (NER) is an essential mechanism for single-strand breaks (SSB) repair while xeroderma pigmentosum family (XPA to XPG) is the most important system to NER. Myelodysplastic syndrome (MDS) is a heterogeneous hematological cancer characterized by cytopenias and risk of...

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Autores principales: Borges, Daniela de Paula, dos Santos, Rinna Maria Arruda Rodrigues, Velloso, Elvira Rodrigues Pereira, Ribeiro Junior, Howard Lopes, Larripa, Irene Beatriz, Camacho, Maria Fernanda, González, Jacqueline, Pratx, Leandro Daniel Burgos, Magalhães, Sílvia Maria Meira, Belli, Carolina Bárbara, Pinheiro, Ronald Feitosa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Sociedade Brasileira de Hematologia e Hemoterapia 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10244233/
https://www.ncbi.nlm.nih.gov/pubmed/34544665
http://dx.doi.org/10.1016/j.htct.2021.08.002
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author Borges, Daniela de Paula
dos Santos, Rinna Maria Arruda Rodrigues
Velloso, Elvira Rodrigues Pereira
Ribeiro Junior, Howard Lopes
Larripa, Irene Beatriz
Camacho, Maria Fernanda
González, Jacqueline
Pratx, Leandro Daniel Burgos
Magalhães, Sílvia Maria Meira
Belli, Carolina Bárbara
Pinheiro, Ronald Feitosa
author_facet Borges, Daniela de Paula
dos Santos, Rinna Maria Arruda Rodrigues
Velloso, Elvira Rodrigues Pereira
Ribeiro Junior, Howard Lopes
Larripa, Irene Beatriz
Camacho, Maria Fernanda
González, Jacqueline
Pratx, Leandro Daniel Burgos
Magalhães, Sílvia Maria Meira
Belli, Carolina Bárbara
Pinheiro, Ronald Feitosa
author_sort Borges, Daniela de Paula
collection PubMed
description Nucleotide excision repair pathway (NER) is an essential mechanism for single-strand breaks (SSB) repair while xeroderma pigmentosum family (XPA to XPG) is the most important system to NER. Myelodysplastic syndrome (MDS) is a heterogeneous hematological cancer characterized by cytopenias and risk of acute myeloid leukemia (AML) transformation. MDS pathogenesis has been associated with problems of DNA repair system. This report aimed to evaluate NER polymorphisms (XPA rs1800975, XPC rs2228000, XPD rs1799793 and XPF rs1800067) in 269 MDS patients of different populations in Latin America (173 Brazilian and 96 Argentinean). Genotypes were identified in DNA samples by RT-qPCR using TaqMan SNP Genotyping Assay. Regarding rs1799793 polymorphism of XPD for Brazilian population, the heterozygous genotype AG presented a high odds ratio (OR) to have a normal karyotype (p = 0.012, OR=3.000) and the mutant homozygous genotype AA was associated to a high OR of AML transformation (p = 0.034, OR=7.4). In Argentine population, the homozygous mutant AA genotype of rs1800975 polymorphism of XPA was associated with an increased odd to have hemoglobin levels below 8g/dL (p = 0.013, OR=10.000) while for the rs1799793 polymorphism of XPD, the heterozygous AG genotype decreased OR to be classified as good (p < 0.001, OR=9.05 × 10(−10)), and intermediate (p < 0.001, OR=3.08 × 10(−10)), according to Revised-International Prognostic Scoring System. Regarding the rs1800067 polymorphisms of XPF, the homozygous mutant AA genotype showed a decreased OR to be classified as good (p < 0.001, OR=4.03 × 10(−13)) and intermediate (p < 0.001, OR=2.54 × 10(−13)). Our report reinforces the heterogeneity of MDS and demonstrates the importance of ethnic differences and regional influences in pathogenesis and prognosis of MDS.
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spelling pubmed-102442332023-06-08 Functional polymorphisms of DNA repair genes in Latin America reinforces the heterogeneity of Myelodysplastic Syndrome Borges, Daniela de Paula dos Santos, Rinna Maria Arruda Rodrigues Velloso, Elvira Rodrigues Pereira Ribeiro Junior, Howard Lopes Larripa, Irene Beatriz Camacho, Maria Fernanda González, Jacqueline Pratx, Leandro Daniel Burgos Magalhães, Sílvia Maria Meira Belli, Carolina Bárbara Pinheiro, Ronald Feitosa Hematol Transfus Cell Ther Original Article Nucleotide excision repair pathway (NER) is an essential mechanism for single-strand breaks (SSB) repair while xeroderma pigmentosum family (XPA to XPG) is the most important system to NER. Myelodysplastic syndrome (MDS) is a heterogeneous hematological cancer characterized by cytopenias and risk of acute myeloid leukemia (AML) transformation. MDS pathogenesis has been associated with problems of DNA repair system. This report aimed to evaluate NER polymorphisms (XPA rs1800975, XPC rs2228000, XPD rs1799793 and XPF rs1800067) in 269 MDS patients of different populations in Latin America (173 Brazilian and 96 Argentinean). Genotypes were identified in DNA samples by RT-qPCR using TaqMan SNP Genotyping Assay. Regarding rs1799793 polymorphism of XPD for Brazilian population, the heterozygous genotype AG presented a high odds ratio (OR) to have a normal karyotype (p = 0.012, OR=3.000) and the mutant homozygous genotype AA was associated to a high OR of AML transformation (p = 0.034, OR=7.4). In Argentine population, the homozygous mutant AA genotype of rs1800975 polymorphism of XPA was associated with an increased odd to have hemoglobin levels below 8g/dL (p = 0.013, OR=10.000) while for the rs1799793 polymorphism of XPD, the heterozygous AG genotype decreased OR to be classified as good (p < 0.001, OR=9.05 × 10(−10)), and intermediate (p < 0.001, OR=3.08 × 10(−10)), according to Revised-International Prognostic Scoring System. Regarding the rs1800067 polymorphisms of XPF, the homozygous mutant AA genotype showed a decreased OR to be classified as good (p < 0.001, OR=4.03 × 10(−13)) and intermediate (p < 0.001, OR=2.54 × 10(−13)). Our report reinforces the heterogeneity of MDS and demonstrates the importance of ethnic differences and regional influences in pathogenesis and prognosis of MDS. Sociedade Brasileira de Hematologia e Hemoterapia 2023 2021-09-09 /pmc/articles/PMC10244233/ /pubmed/34544665 http://dx.doi.org/10.1016/j.htct.2021.08.002 Text en © 2021 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier España, S.L.U. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Borges, Daniela de Paula
dos Santos, Rinna Maria Arruda Rodrigues
Velloso, Elvira Rodrigues Pereira
Ribeiro Junior, Howard Lopes
Larripa, Irene Beatriz
Camacho, Maria Fernanda
González, Jacqueline
Pratx, Leandro Daniel Burgos
Magalhães, Sílvia Maria Meira
Belli, Carolina Bárbara
Pinheiro, Ronald Feitosa
Functional polymorphisms of DNA repair genes in Latin America reinforces the heterogeneity of Myelodysplastic Syndrome
title Functional polymorphisms of DNA repair genes in Latin America reinforces the heterogeneity of Myelodysplastic Syndrome
title_full Functional polymorphisms of DNA repair genes in Latin America reinforces the heterogeneity of Myelodysplastic Syndrome
title_fullStr Functional polymorphisms of DNA repair genes in Latin America reinforces the heterogeneity of Myelodysplastic Syndrome
title_full_unstemmed Functional polymorphisms of DNA repair genes in Latin America reinforces the heterogeneity of Myelodysplastic Syndrome
title_short Functional polymorphisms of DNA repair genes in Latin America reinforces the heterogeneity of Myelodysplastic Syndrome
title_sort functional polymorphisms of dna repair genes in latin america reinforces the heterogeneity of myelodysplastic syndrome
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10244233/
https://www.ncbi.nlm.nih.gov/pubmed/34544665
http://dx.doi.org/10.1016/j.htct.2021.08.002
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