Abstract
This study aimed to explore the associations between the TP53 rs1042522 (TP53 Arg72Pro), MDM2 rs2279744 (MDM2 309T>G), rs3730485 (MDM2 del1518), MDM4 rs4245739 (MDM4 34091 C>A) variants and odds of developing acute myeloid leukemia (AML) in a cohort of 809 adult subjects, consisting of 406 healthy controls and 403 AML patients. Model-based multifactor dimensionality reduction (MB-MDR) framework was used to identify the interactions of the mentioned variants and their association with AML risk. Associations of the mentioned variants with clinical features of AML, somatic mutations, and response to treatment were also evaluated. Significant associations between TP53 rs1042522 and MDM4 rs4245739 variants and AML susceptibility were noticed. MB-MDR and logistic regression analysis revealed an interaction between MDM2 rs2279744 and TP53 rs1042522, between MDM4 rs4245739 and MDM2 rs3730485, as well as significant associations with AML susceptibility. Several associations between the mentioned variants and clinical features of AML and somatic mutations were also noticed. Individually, the variant genotypes of TP53 rs1042522 and MDM4 rs4245739 were associated with AML susceptibility, but their interaction with MDM2 rs2279744 and rs3730485 modulated the risk for AML. The variant genotypes of TP53 rs1042522 were associated with adverse molecular and cytogenetic risk and also with NPM1 mutations.
Highlights
Acute myeloid leukemia (AML) patients may have one or several genetic abnormalities
Our study aimed to explore the associations between the Tumor protein p53 (TP53) rs1042522 (TP53 Arg72Pro), Mouse double minute 2 homolog (MDM2) rs2279744 (MDM2 309T>G), rs3730485 (MDM2 del1518), and MDM4 rs4245739 (MDM4 34091 C>A) variants and odds of developing AML in a cohort of 809 adult subjects, consisting of 406 healthy controls and 403 AML patients
There was a significant difference in sex distribution between these two groups (p = 0.013), male individuals being more frequent in the AML group than in the control group (215, 53.34% versus 181, 44.58%) with a male-to-female ratio of 1.14 for AML group
Summary
Acute myeloid leukemia (AML) patients may have one or several genetic abnormalities. More than 90% of the AML patients had genetic abnormalities. The genetic alteration involved Tumor protein p53 (TP53) gene. This gene has an important role in apoptosis and DNA-damage response [1]. TP53 gene expression is inhibited by Mouse double minute 2 homolog (MDM2) gene and by MDM4 gene (homolog of MDM2) [2,3], MDM2, and MDM4 genes being negative regulators of p53 [4]
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have