The association of avascular necrosis with vitamin D receptor gene polymorphism and its role in diagnosing asymptomatic avascular necrosis in children with acute lymphoblastic leukemia

The Association of Avascular Necrosis with Vitamin D Receptor Gene Polymorphism and Its Role in Diagnosing Asymptomatic Avascular Necrosis in Children with Acute Lymphoblastic Leukemia Background and Purpose: Avascular necrosis was seen to be an important complication in patients with acute lymphoblastic leukemia. It is thought to develop both due to leukemic process itself and also due to cellular toxicity and vascular damage of chemotherapies including corticosteroid treatment. Our study aims to determine the association between avascular necrosis development and vitamin D receptor gene polymorphism in acute lymphoblastic leukemia patients, and to benefit from the results obtained in this study. Method and Material: The study included 71 acute lymphoblastic leukemia patients aged 0-18 years, who were treated at Pediatric Hematology-Oncology departments of Bezmi Alem Vakıf University Medical Facultyand Oncology Institute of Istanbul UniversityMedical Faculty. Deoxyribonucleic acid was isolated from blood samples and polymorphisms at vitamin D receptor gene sites BsmI, ApaI ve TaqI were established via the polymerase chain reaction-restriction fragment length polymorphism method. Calcium, phosphor, alkalinephosphatase, 25 hydroxy vitamin D, 1,25- hydroxyvitamin D were studied as biochemical parameters. Results: 1. There was no significant statistical relationship between avascular necrosis development and BsmI, ApaI, TaqI polymorphisms in acute lymphoblastic leukemia patients in our study (respectively p=0.819, p=0.731, p=0.623). 2. There was a significant relationship between higher age at acute lymphoblastic leukemia diagnosis and avascular necrosis (p<0.001). 3. Female gender was significantly higher among avascular necrosis patients (p<0.05). 4 4. Joint involvements of the hip, knee and ankle were significantly higher in patients with avascular necrosis. 5. There was no significant statistical relationship between avascular necrosis development and calcium, alkaline phosphatase, 25 hydroxy vitamin D and 1,25- hydroxy vitamin D parameters. 6. Phosphorus was found to be significantly low in avascular necrosis group compared to asymptomatic avascular necrosis group. 7. All patients who underwent surgery for avascular necrosis were all females and had hip joint involvement. Conclusion: In our study, BsmI, ApaI, TaqI polymorphisms in the vitamin D receptor gene were not associated with avascular necrosis development in acute lymphoblastic leukemia patients. However, the ratio of asymptomatic lesions is high, thus early diagnosis and treatment is of great importance. Personolized therapy is getting increasingly important in acute lymphoblastic leukemia treatment, and specifically pharmacogenetic risk factors probably important in terms of treatment outcome should be investigated prospectively in comprehensive studies .