Association of XPD (Lys751Gln) and XRCC1 (Arg280His) gene polymorphisms in myelodysplastic syndrome

Ann Hematol. 2016 Jan;95(1):79-85. doi: 10.1007/s00277-015-2528-3.


Myelodysplastic syndromes (MDSs) are heterogeneous hematopoietic disease characterized by ineffective haematopoiesis that frequently transforms into acute leukaemia. Alterations in many individual biologic pathways have been reported in MDS pathophysiology. Disease progression along the MDS, acute myeloid leukemia (AML) continuum is believed to be a consequence of stepwise accumulation of DNA mutations which infers a defect in DNA repair. The present study investigated the association between DNA repair genes (XRCC1, XRCC3, OGG1, XPD and RAD51) and the risk of developing MDS. The study was carried out in 92 primary MDS patients. The genotyping study was carried out by PCR-RFLP technique. We have studied seven single-nucleotide polymorphisms (SNPs) of five DNA repair genes (XRCC1 (Arg194Trp, Arg280His, Arg399Gln), XRCC3, XPD, RAD51 and OGG1). Significantly, a high frequency of DNA repair gene XRCC1 (Arg280His) (p=0.05) and XPD (Lys751Gln) (p=0.01) polymorphism was observed in MDS patients compared to controls. The distribution of polymorphisms in MDS subgroups showed a significant association of XRCC1 with RAEB I compared to other subgroup. Though a high frequency of XRCC1 gene polymorphism was observed in farmers and tobacco chewers, it was not statistically significant. Our study suggests that XRCC1 (Arg280His) and XPD polymorphisms are associated with risk of MDS and XRCC1 polymorphism strongly associated with advanced MDS subgroup. Hence, these polymorphisms can be used as a prognostic marker in MDS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Arginine / genetics
  • Case-Control Studies
  • DNA-Binding Proteins / genetics*
  • Female
  • Genetic Association Studies* / methods
  • Glutamine / genetics
  • Histidine / genetics
  • Humans
  • Lysine / genetics
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / diagnosis*
  • Myelodysplastic Syndromes / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • X-ray Repair Cross Complementing Protein 1
  • Xeroderma Pigmentosum Group D Protein / genetics*
  • Young Adult


  • DNA-Binding Proteins
  • X-ray Repair Cross Complementing Protein 1
  • XRCC1 protein, human
  • Glutamine
  • Histidine
  • Arginine
  • Xeroderma Pigmentosum Group D Protein
  • ERCC2 protein, human
  • Lysine