Down regulation of DNA repair genes Lig4, Ku70, Ku80, XRCC3 in primary myelodysplastic syndromes

The myelodysplastic syndrome (MDS) is characterized by genetic instability which is associated with abnormal DNA repair mechanisms. The expression of ten DNA repair genes (Ku70, Ku80, Lig4, OGG1, Apex1, PARP 1, XPA, PMS1, XRCC3, RAD18) were studied in 68 karyotypically normal MDS patients. The expression of Lig4, Ku70, Ku80 and XRCC3 genes was significantly (P < 0.05) down regulated in MDS patients compared to controls. Lig4 and XRCC3 gene was down regulated 6 to 7 fold in MDS RAEB-I and RAEB-II subgroups compared to other subgroups. We have correlated the expression results with occupational exposure and habits of MDS. Patients that were exposed to polyvinyl chloride showed significantly low expression (6 folds) of Ku80 gene, whereas patients having the habit of tobacco chewing showed low expression (4-5 fold) of Lig4, Ku70, Ku80 and XRCC3 gene. Our study suggests that the DNA repair genes that are involved in NHEJ (Lig4, Ku70, Ku80) and HR (XRCC3) repair mechanism are associated with the MDS.