Polymorphism in Myeloperoxidase Gene of BRONJ Patients

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a complication seen in patients on bisphosphonates (BPs) for malignant diseases such as cancer and serious conditions including osteoporosis. Oral, periodontal, or endodontic treatment has been implicated as possible risk factors of BRONJ for those taking BPs. Studies indicate that patients taking BPs are at a higher risk of developing BRONJ. We hypothesize that genetic and environmental factors may contribute to the development of the disease given that several patients who have taken BPs have not developed BRONJ. A weakened microbicidal activity of the immune cells could be one of the factors attributable to the etiology of ONJ. One important human defense mechanism is myeloperoxidase (MPO) system, found in leukocytes that interact with hydrogen peroxide and halide to defend the human cells from bacteria, fungi, and viruses.  Recent studies have identified polymorphisms in MPO gene, thus strengthening our hypothesis to analyze MPO gene. Objective: To identify polymorphisms in MPO gene of BRONJ patients.  Methods: Tissue samples for this study included 15 patients, 5 each from BP⁺ONJ⁺, BP⁺ONJ^-, and BP^-ONJ^- cohorts. DNA was extracted from each tissue sample followed by the amplification of the 350 bp MPO region by polymerase chain reaction. Agarose gel electrophoresis was performed to confirm the size of the amplicons. Restriction fragment length polymorphism (RFLP) was conducted to detect the presence of mutations in MPO gene and was further confirmed through DNA sequencing. Results: The data from DNA sequencing and RFLP was analyzed for any polymorphisms in MPO gene. RFLP results indicated that two of the patients showed heterozygous genotype and the remaining homozygous.  Conclusions: A mutation in MPO gene would suggest that hereditary genetic factors could be one of the reasons for developing chronic infection of BRONJ. The funding was provided by NYU student research funds.