Polymorphisms in genes implicated in base excision repair (BER) pathway are associated with susceptibility to Paget's disease of bone.

Paget's disease of bone (PDB) is a chronic bone metabolic disorder. Currently, PDB is the second most frequent bone disorder. PDB is a focal disorder affecting the skeleton segmentally but the cause of which is unknown. It has been hypothesised that somatic mutations could be responsible for the mosaicism described in PDB patients. Therefore, our hypothesis is that defective response to DNA damage may lead to somatic mutations favouring an increased risk of PDB. So that we have analysed polymorphisms in DNA repair genes involved in the BER, NER and DSBR pathways in order to evaluate the role of these variants in modulating PDB risk. We found statistically significant differences in genotypic and allelic distribution for polymorphisms in genes implicated in the BER pathway. Our results showed that carrying the allele T of XRCC1 rs1799782 polymorphism and the allele G of APEX rs1130409 polymorphism increased the risk of developing PDB. These polymorphisms could cause a lower DNA repair efficiency and this might lead to local somatic mutations favouring bone metabolic alterations characteristic of PDB. This is the first report showing an association between polymorphism in genes implicated in the BER pathway with PDB.