The synergistic effect of HIF-1α, VEGFA and VEGFR2 gene polymorphisms in the pathogenesis of acute myeloid leukemia

Abstract

Objectives

This study aims to analyze polymorphisms and the differential mRNA expression of some hypoxia-angiogenesis pathway genes in acute myeloid leukemia (AML) cases and correlate these findings with disease pathogenesis.

Patients and methods

The study included 64 de novo AML cases with mean age of 29.45 ± 16.49 years and sex ratio of 1.46:1.00; along with 64 age and sex-matched controls. With specific standardized primers and Taq polymerase enzyme, the targeted genes were amplified using PCR. Further RFLP analysis was done using specific restriction endonuclease enzymes to detect polymorphisms. Semi-quantitative real-time PCR was performed for gene expression studies at mRNA level.

Results

Higher prevalence of CT and TT genotypes of HIF-1α rs11549465 SNP, CA and AA genotypes of VEGFA rs699947 SNP and AT and TT genotypes of VEGFR2 rs1870377 SNP were found in cases as compared to control. The co-occurrence of T allele of HIF-1α rs11549465, A allele of VEGFA rs699947 and T allele of VEGFR2 rs1870377 SNPs were found to be common in cases indicating higher risk of the disease. mRNA expression analysis revealed upregulation of HIF-1α, VEGFA and VEGFR2 by 9.92 ± 7.28, 9.05 ± 5.87 and 2.11 ± 0.48 fold respectively in patients. Significant correlation (p < 0.01) was found between the expression of HIF-1α and VEGFA genes. Correlation analysis between genotypes and mRNA expression profiles detected the role of T allele of HIF-1α rs11549465 SNP, A allele of VEGFA rs699947 SNP and AT genotype of VEGFR2 rs1870377 SNP in the overexpression of respective genes.

Conclusion

Synergistic association of T allele of HIF-1α rs11549465, A allele of VEGFA rs699947 and AT genotype of VEGFR2 rs1870377 SNPs have been identified that might promote the pathogenesis of AML.