Abstract

Increased angiogenesis, mediated by vascular endothelial growth factor (VEGF), was associated with poor prognosis in acute myeloid leukaemia (AML) patients. The current study investigated the impact of VEGF gene (VEGFA) single nucleotide polymorphisms (SNPs) on treatment outcomes for AML. Four VEGFA SNPs were analysed for -2578C>A (rs699947), -460T>C (rs833061), +405G>C (rs2010963) and +936 C>T (rs3025039) loci in 138 AML patients. The +936 CC/CT genotype showed strong correlation with favourable leukaemia-free survival (LFS) at 2 years (51.3%) versus with +936 CC genotype (33.6%, P = 0.03). Strong linkage disequilibrium was noted among loci -2578, -460 and +405, but not with +936. Accordingly, four haplotypes were generated based on the genotypes of -2578, -460 and +405 as follows: CTC (40.2%), CTG (35.0%), ACG (22.0%) and ATC (1.2%). The LFS and event-free survival (EFS) inversely correlated with CTG haplotype (P = 0.03 for LFS; P = 0.05 for EFS). We scored the VEGFA polymorphism marker based on +936 C>T genotype and CTG haplotype for -2578, -460 and +405, which demonstrated a good correlation with the treatment outcomes: LFS (P = 0.01), EFS (P = 0.03) and overall survival (P = 0.01). The VEGFA +936 C>T genotype and CTG haplotype seemed to have an additive effect to predict the prognosis in AML patients.

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