A polymorphism in the TYMP gene is associated with the outcome of HLA-identical sibling allogeneic stem cell transplantation
Por:
Guillem, V, Hernandez-Boluda, JC, Gallardo, D, Buno, I, Bosch, A, Martinez-Laperche, C, de la Camara, R, Brunet, S, Martin, C, Nieto, JB, Martinez, C, Perez, A, Montoro, J, Garcia-Noblejas, A, Solano, C
Publicada:
1 oct 2013
Resumen:
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 survivalcarriers 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. (c) 2013 Wiley Periodicals, Inc.
Filiaciones:
Guillem, V:
Univ Valencia, Dept Hematol & Med Oncol, Hosp Clin Univ Valencia, Inst Invest Sanitaria INCLIVA, Valencia, Spain
Hernandez-Boluda, JC:
Univ Valencia, Dept Hematol & Med Oncol, Hosp Clin Univ Valencia, Inst Invest Sanitaria INCLIVA, Valencia, Spain
Gallardo, D:
Hosp Josep Trueta, IDIBGI Fdn, Hematol Serv, ICO Girona, Girona, Spain
Buno, I:
Hosp Gen Univ Gregorio Maranon, Hematol Serv, Inst Invest Sanitaria Gregorio Maranon, Madrid, Spain
Bosch, A:
Hosp Josep Trueta, IDIBGI Fdn, Hematol Serv, ICO Girona, Girona, Spain
Martinez-Laperche, C:
Hosp Gen Univ Gregorio Maranon, Hematol Serv, Inst Invest Sanitaria Gregorio Maranon, Madrid, Spain
de la Camara, R:
Hosp La Princesa, Hematol Serv, Madrid, Spain
Brunet, S:
Hosp Santa Creu & Sant Pau, Dept Clin Hematol, Barcelona, Spain
Martin, C:
Hosp Reina Sofia, Hematol Serv, Cordoba, Spain
Nieto, JB:
Hosp Morales Meseguer, Hematol Serv, Murcia, Spain
Martinez, C:
Hosp Clin Barcelona, Hematol Serv, Barcelona, Spain
Perez, A:
Univ Valencia, Dept Hematol & Med Oncol, Hosp Clin Univ Valencia, Inst Invest Sanitaria INCLIVA, Valencia, Spain
Montoro, J:
Univ Valencia, Dept Hematol & Med Oncol, Hosp Clin Univ Valencia, Inst Invest Sanitaria INCLIVA, Valencia, Spain
Garcia-Noblejas, A:
Hosp La Princesa, Hematol Serv, Madrid, Spain
Solano, C:
Univ Valencia, Dept Hematol & Med Oncol, Hosp Clin Univ Valencia, Inst Invest Sanitaria INCLIVA, Valencia, Spain
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