A polymorphism in the TYMP gene is associated with the outcome of HLA-identical sibling allogeneic stem cell transplantation

Vicent Guillem, Juan Carlos Hernández-Boluda, David Gallardo, Ismael Buño, Anna Bosch, Carolina Martínez-Laperche, Rafael de la Cámara, Salut Brunet, Carmen Martin, José B. Nieto, Carmen Martínez, Ariadna Pérez, Juan Montoro, Ana Garcia-Noblejas, Carlos Solano

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Thymidine phosphorylase (TYMP), an enzyme involved in nucleotide synthesis, has been implicated in critical biological processes such as DNA replication, protection against mutations, and tissue repair. In this work, we retrospectively evaluated the influence of a polymorphism in the TYMP gene (rs112723255; G/A) upon the outcome of 448 patients subjected to allogeneic stem cell transplantation (allo-SCT) from an human leukocyte antigen (HLA)-identical sibling donor. The TYMP genotype of patients correlated with overall survival-carriers of the minor allele (A) being at an increased risk of dying after transplantation (hazard ratio, HR=1.9; P=0.004). This effect was mostly due to differences in transplant toxicity-related mortality (HR=2.5; P=0.029). In addition, the TYMP genotype of donors was associated with the risk of chronic graft-versus-host disease (GVHD)-carriers of the minor allele being at an increased risk of developing this complication ([HR]=1.7; P=0.039). The impact of such polymorphism on the risk of chronic GVHD is limited to patients transplanted in early stage disease (HR=2.2; P=0.019). The combination of a donor harboring the minor allele with a patient homozygous for the major allele was associated with the highest risk of chronic GVHD (HR=2.8; P=0.008). These findings provide the first evidence of the significant impact of the TYMP genotype upon the clinical outcome of patients treated with HLA-identical sibling allo-SCT. Am. J. Hematol. 88:883-889, 2013.

Original languageEnglish
Pages (from-to)883-889
Number of pages7
JournalAmerican Journal of Hematology
Volume88
Issue number10
DOIs
Publication statusPublished - Oct 2013

Fingerprint

Thymidine Phosphorylase
Stem Cell Transplantation
HLA Antigens
Siblings
Graft vs Host Disease
Alleles
Genes
Genotype
Tissue Donors
Biological Phenomena
DNA Replication
Nucleotides
Transplantation
Transplants
Mutation
Survival
Mortality
Enzymes

ASJC Scopus subject areas

  • Hematology

Cite this

Guillem, V., Hernández-Boluda, J. C., Gallardo, D., Buño, I., Bosch, A., Martínez-Laperche, C., ... Solano, C. (2013). A polymorphism in the TYMP gene is associated with the outcome of HLA-identical sibling allogeneic stem cell transplantation. American Journal of Hematology, 88(10), 883-889. https://doi.org/10.1002/ajh.23523

A polymorphism in the TYMP gene is associated with the outcome of HLA-identical sibling allogeneic stem cell transplantation. / Guillem, Vicent; Hernández-Boluda, Juan Carlos; Gallardo, David; Buño, Ismael; Bosch, Anna; Martínez-Laperche, Carolina; de la Cámara, Rafael; Brunet, Salut; Martin, Carmen; Nieto, José B.; Martínez, Carmen; Pérez, Ariadna; Montoro, Juan; Garcia-Noblejas, Ana; Solano, Carlos.

In: American Journal of Hematology, Vol. 88, No. 10, 10.2013, p. 883-889.

Research output: Contribution to journalArticle

Guillem, V, Hernández-Boluda, JC, Gallardo, D, Buño, I, Bosch, A, Martínez-Laperche, C, de la Cámara, R, Brunet, S, Martin, C, Nieto, JB, Martínez, C, Pérez, A, Montoro, J, Garcia-Noblejas, A & Solano, C 2013, 'A polymorphism in the TYMP gene is associated with the outcome of HLA-identical sibling allogeneic stem cell transplantation', American Journal of Hematology, vol. 88, no. 10, pp. 883-889. https://doi.org/10.1002/ajh.23523
Guillem, Vicent ; Hernández-Boluda, Juan Carlos ; Gallardo, David ; Buño, Ismael ; Bosch, Anna ; Martínez-Laperche, Carolina ; de la Cámara, Rafael ; Brunet, Salut ; Martin, Carmen ; Nieto, José B. ; Martínez, Carmen ; Pérez, Ariadna ; Montoro, Juan ; Garcia-Noblejas, Ana ; Solano, Carlos. / A polymorphism in the TYMP gene is associated with the outcome of HLA-identical sibling allogeneic stem cell transplantation. In: American Journal of Hematology. 2013 ; Vol. 88, No. 10. pp. 883-889.
@article{a8eae1f34a4f4bc59a78dd5b516c8598,
title = "A polymorphism in the TYMP gene is associated with the outcome of HLA-identical sibling allogeneic stem cell transplantation",
abstract = "Thymidine phosphorylase (TYMP), an enzyme involved in nucleotide synthesis, has been implicated in critical biological processes such as DNA replication, protection against mutations, and tissue repair. In this work, we retrospectively evaluated the influence of a polymorphism in the TYMP gene (rs112723255; G/A) upon the outcome of 448 patients subjected to allogeneic stem cell transplantation (allo-SCT) from an human leukocyte antigen (HLA)-identical sibling donor. The TYMP genotype of patients correlated with overall survival-carriers of the minor allele (A) being at an increased risk of dying after transplantation (hazard ratio, HR=1.9; P=0.004). This effect was mostly due to differences in transplant toxicity-related mortality (HR=2.5; P=0.029). In addition, the TYMP genotype of donors was associated with the risk of chronic graft-versus-host disease (GVHD)-carriers of the minor allele being at an increased risk of developing this complication ([HR]=1.7; P=0.039). The impact of such polymorphism on the risk of chronic GVHD is limited to patients transplanted in early stage disease (HR=2.2; P=0.019). The combination of a donor harboring the minor allele with a patient homozygous for the major allele was associated with the highest risk of chronic GVHD (HR=2.8; P=0.008). These findings provide the first evidence of the significant impact of the TYMP genotype upon the clinical outcome of patients treated with HLA-identical sibling allo-SCT. Am. J. Hematol. 88:883-889, 2013.",
author = "Vicent Guillem and Hern{\'a}ndez-Boluda, {Juan Carlos} and David Gallardo and Ismael Bu{\~n}o and Anna Bosch and Carolina Mart{\'i}nez-Laperche and {de la C{\'a}mara}, Rafael and Salut Brunet and Carmen Martin and Nieto, {Jos{\'e} B.} and Carmen Mart{\'i}nez and Ariadna P{\'e}rez and Juan Montoro and Ana Garcia-Noblejas and Carlos Solano",
year = "2013",
month = "10",
doi = "10.1002/ajh.23523",
language = "English",
volume = "88",
pages = "883--889",
journal = "American Journal of Hematology",
issn = "0361-8609",
publisher = "Wiley-Liss Inc.",
number = "10",

}

TY - JOUR

T1 - A polymorphism in the TYMP gene is associated with the outcome of HLA-identical sibling allogeneic stem cell transplantation

AU - Guillem, Vicent

AU - Hernández-Boluda, Juan Carlos

AU - Gallardo, David

AU - Buño, Ismael

AU - Bosch, Anna

AU - Martínez-Laperche, Carolina

AU - de la Cámara, Rafael

AU - Brunet, Salut

AU - Martin, Carmen

AU - Nieto, José B.

AU - Martínez, Carmen

AU - Pérez, Ariadna

AU - Montoro, Juan

AU - Garcia-Noblejas, Ana

AU - Solano, Carlos

PY - 2013/10

Y1 - 2013/10

N2 - Thymidine phosphorylase (TYMP), an enzyme involved in nucleotide synthesis, has been implicated in critical biological processes such as DNA replication, protection against mutations, and tissue repair. In this work, we retrospectively evaluated the influence of a polymorphism in the TYMP gene (rs112723255; G/A) upon the outcome of 448 patients subjected to allogeneic stem cell transplantation (allo-SCT) from an human leukocyte antigen (HLA)-identical sibling donor. The TYMP genotype of patients correlated with overall survival-carriers of the minor allele (A) being at an increased risk of dying after transplantation (hazard ratio, HR=1.9; P=0.004). This effect was mostly due to differences in transplant toxicity-related mortality (HR=2.5; P=0.029). In addition, the TYMP genotype of donors was associated with the risk of chronic graft-versus-host disease (GVHD)-carriers of the minor allele being at an increased risk of developing this complication ([HR]=1.7; P=0.039). The impact of such polymorphism on the risk of chronic GVHD is limited to patients transplanted in early stage disease (HR=2.2; P=0.019). The combination of a donor harboring the minor allele with a patient homozygous for the major allele was associated with the highest risk of chronic GVHD (HR=2.8; P=0.008). These findings provide the first evidence of the significant impact of the TYMP genotype upon the clinical outcome of patients treated with HLA-identical sibling allo-SCT. Am. J. Hematol. 88:883-889, 2013.

AB - Thymidine phosphorylase (TYMP), an enzyme involved in nucleotide synthesis, has been implicated in critical biological processes such as DNA replication, protection against mutations, and tissue repair. In this work, we retrospectively evaluated the influence of a polymorphism in the TYMP gene (rs112723255; G/A) upon the outcome of 448 patients subjected to allogeneic stem cell transplantation (allo-SCT) from an human leukocyte antigen (HLA)-identical sibling donor. The TYMP genotype of patients correlated with overall survival-carriers of the minor allele (A) being at an increased risk of dying after transplantation (hazard ratio, HR=1.9; P=0.004). This effect was mostly due to differences in transplant toxicity-related mortality (HR=2.5; P=0.029). In addition, the TYMP genotype of donors was associated with the risk of chronic graft-versus-host disease (GVHD)-carriers of the minor allele being at an increased risk of developing this complication ([HR]=1.7; P=0.039). The impact of such polymorphism on the risk of chronic GVHD is limited to patients transplanted in early stage disease (HR=2.2; P=0.019). The combination of a donor harboring the minor allele with a patient homozygous for the major allele was associated with the highest risk of chronic GVHD (HR=2.8; P=0.008). These findings provide the first evidence of the significant impact of the TYMP genotype upon the clinical outcome of patients treated with HLA-identical sibling allo-SCT. Am. J. Hematol. 88:883-889, 2013.

UR - http://www.scopus.com/inward/record.url?scp=84884711636&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84884711636&partnerID=8YFLogxK

U2 - 10.1002/ajh.23523

DO - 10.1002/ajh.23523

M3 - Article

C2 - 23813863

AN - SCOPUS:84884711636

VL - 88

SP - 883

EP - 889

JO - American Journal of Hematology

JF - American Journal of Hematology

SN - 0361-8609

IS - 10

ER -