Genetic polymorphism of vitamin D receptors and plasminogen activator inhibitor‐1 and osteonecrosis risk in childhood acute lymphoblastic leukemia

Abstract

Background Osteonecrosis (ON) is one of the major therapy‐related complications in childhood acute lymphoblastic leukemia (ALL). The purpose of the current study is to assess the frequency of ON in children with ALL and to detect whether polymorphisms in vitamin D receptor gene (VDR) and plasminogen activator inhibitor‐1 (PAI‐1) gene can affect the risk of ON. Patients and Methods Nighty‐six ALL children were enrolled. Serum 25‐hydroxyvitamin D 25(OH)D levels were performed in addition to the detection of polymorphisms in PAI‐1and VDR genes by polymerase chain reaction. Results Ten out of 96 patients had ON (four males and six females aged above 10 years) and had an insufficient level of 25(OH)D. Fifty‐two percent of patients had PAI‐1 GG genotype while 48% had PAI‐1 GA genotype. PAI‐1 polymorphism was detected in 60% of all ON cases. The frequencies of VDR genotypes were CT (56.3%), CC (39.6%), and TT (4.2%). Osteonecrosis was found in eight patients with CC genotype and in two patients with CT genotype. Conclusion Osteonecrosis can develop early during the therapy of ALL. Older age and insufficient level of 25(OH)D were considered important risk factor for the development of osteonecrosis. PAT‐1 and VDR gene polymorphism may be a genetic risk factor in its pathogenesis.

BMP6 and VDR gene polymorphisms are associated with osteonecrosis in a sickle cell anaemia cohort

“…rs2228570 TT genotype was previously reported as a protector factor for discopathies and osteochondrosis development in patients with lumbar spine pathologies 24 . Moreover, in children with acute lymphoblastic leukaemia, the rs2228570 CC genotype was associated with a higher frequency of osteonecrosis 22,44 …”

“…24 Moreover, in children with acute lymphoblastic leukaemia, the rs2228570 CC genotype was associated with a higher frequency of osteonecrosis. 22,44 While functional associations have been delineated, it is important to note that the interactions of both VDR rs2228570 isoforms may vary significantly depending on the specific tissue and target gene in question. 45 The decreased VDR efficiency associated with the rs2228570 T allele might induce the synthesis of vitamin D levels, contributing to healthier bone metabolism.…”

Analysis of factors affecting the clinical efficacy and quality of life in the treatment of pediatric acute lymphoblastic leukemia

“…ALL used to be refractory with a high clinical mortality rate, but now it has witnessed a significant increase in the cure rate with the improvement of medical technology and the availability of more treatment methods. Studies have shown 15 that about 95% of children with ALL are in complete remission after treatment, and the 5-year survival rate in developed countries is greater than 90% 16 , which has also been increased to 80.0%-90.0% in China. 17 In view of the high heterogeneity of ALL in children, each child with ALL presents its unique clinical characteristics, especially the different clonal subtypes and biological characteristics of ALL, resulting in different responses to treatment and prognosis of children with ALL.…”

Atraumatic osteonecrosis of the humeral head: pathophysiology and current concepts of evaluation and treatment

“… 58 A population with a particularly high risk for CS-induced osteonecrosis are children with acute lymphoblastic lymphoma and leukemia. 70 HHO is an underappreciated adverse late effect of therapy in these patients, which can limit the quality of life and functionality. Two different studies have reported the severity and functional impairment of HHO among children with acute lymphoblastic lymphoma and leukemia.…”

“… 37 , 85 These genes encode glutamate receptor subunits, suggesting a role of the glutamate receptor pathway in the pathogenesis of CS-induced osteonecrosis. 37 In addition, Sherief et al 70 identified that factors strongly associated with CS-induced osteonecrosis, such as older age (>10 years) and lower levels of 25-hydroxy vitamin D, were associated with polymorphisms of the plasminogen activator inhibitor 1 and vitamin D receptor genes. Given that most findings on genetic polymorphisms have not been replicated in independent cohorts, pharmacogenetic testing in clinical practice is not currently indicated.…”