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

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

ASJC Scopus subject areas

  • Hematology

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