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

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Abstract

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.

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Acknowledgments

Author (DJ) thanks the Indian Council of Medical Research (ICMR) for the award of Postdoctoral fellowship. The part of the study was carried out from an ICMR core grant to the institute. Thanks are also due to the haematologists of KEM Hospital and technical staff of the Cytogenetics Department.

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Authors and Affiliations

  1. Department of Cytogenetics, National Institute of Immunohaematology, 13th Floor, New Multistoried Building, KEM Hospital Campus, Parel, Mumbai, 400012, India

    Dolly Joshi, Seema Korgaonkar, Chandrakala Shanmukhaiah & Babu Rao Vundinti

  2. Department of Haematology, KEM Hospital, 10th Floor, New Multistoried Building, Parel, Mumbai, 400012, India

    Chandrakala Shanmukhaiah

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  1. Dolly Joshi
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  2. Seema Korgaonkar
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Correspondence to Babu Rao Vundinti.

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Supplementary Methods 1

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Supplementary Table 1

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Supplementary Fig. 1

PCR-RFLP analysis on 3 % polyacrylamide gel containing ethidium bromide. Arg280His (B) Arg399Gln (C) Arg194Trp polymorphism of XRCC1 gene, (D) Ser326Cys polymorphism of OGG1 (E) Thr241Met polymorphism of XRCC3 (F) 135 G > C polymorphism of RAD51 (G) Lys751Gln polymorphism (JPEG 131 kb).

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Joshi, D., Korgaonkar, S., Shanmukhaiah, C. et al. Association of XPD (Lys751Gln) and XRCC1 (Arg280His) gene polymorphisms in myelodysplastic syndrome. Ann Hematol 95, 79–85 (2016). https://doi.org/10.1007/s00277-015-2528-3

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  • DOI: https://doi.org/10.1007/s00277-015-2528-3

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