Association Analysis of TP53 rs1042522, MDM2 rs2279744, rs3730485, MDM4 rs4245739 Variants and Acute Myeloid Leukemia Susceptibility, Risk Stratification Scores, and Clinical Features: An Exploratory Study.

This study aimed to explore the associations between the rs1042522 ( Arg72Pro), rs2279744 309T>G), rs3730485 del1518), rs4245739 ( 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 rs1042522 and rs4245739 variants and AML susceptibility were noticed. MB-MDR and logistic regression analysis revealed an interaction between rs2279744 and rs1042522, between rs4245739 and 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 rs1042522 and rs4245739 were associated with AML susceptibility, but their interaction with rs2279744 and rs3730485 modulated the risk for AML. The variant genotypes of rs1042522 were associated with adverse molecular and cytogenetic risk and also with mutations.