Tripon Florin, Iancu Mihaela, Trifa Adrian, Crauciuc George Andrei, Boglis Alina, Balla Beata, Cosma Adriana, Dima Delia, Candea Marcela, Lazar Erzsebet, Jimbu Laura, Banescu Claudia
Genetics Department, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540139 Targu Mures, Romania.
Genetics Laboratory, Center for Advanced Medical and Pharmaceutical Research of George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540139 Targu Mures, Romania.
J Clin Med. 2020 Jun 1;9(6):1672. doi: 10.3390/jcm9061672.
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.
本研究旨在探讨809名成年受试者（包括406名健康对照和403名急性髓系白血病患者）队列中，rs1042522（Arg72Pro）、rs2279744（309T>G）、rs3730485（del1518）、rs4245739（34091C>A）变异与急性髓系白血病（AML）发病几率之间的关联。基于模型的多因素降维（MB-MDR）框架用于识别上述变异的相互作用及其与AML风险的关联。还评估了上述变异与AML临床特征、体细胞突变及治疗反应之间的关联。注意到rs1042522和rs4245739变异与AML易感性之间存在显著关联。MB-MDR和逻辑回归分析显示rs2279744与rs1042522之间、rs4245739与rs3730485之间存在相互作用，且与AML易感性存在显著关联。还注意到上述变异与AML临床特征和体细胞突变之间存在多种关联。单独来看，rs1042522和rs4245739的变异基因型与AML易感性相关，但其与rs2279744和rs3730485的相互作用调节了AML风险。rs1042522的变异基因型与不良分子和细胞遗传学风险以及突变也相关。
