Programmed cell death gene polymorphism (rs2227981) as a risk factor in acute myeloid leukemia with and without Splenomegaly

Abstract

Background
Detection of the programmed cell death protein 1 (PD-1) gene polymorphism is important in certain tumor cell subsets.


Aim
This study aimed to evaluate the association between single nucleotide polymorphism PD-1 gene (rs2227981) as a risk factor in acute myeloid leukemia (AML) with and without splenomegaly and to find the relation to patient outcome.


Patients and methods
The study was conducted on 100 patients, 50 of them had proved non-M3-AML in addition to 50 apparently healthy patients were enrolled as a control. The routine laboratory investigations were done as well as immune-phenotyping, cytogenetics study, and detection of PD-1 (rs2227981) genotypes by PCR technique.


Results

The GG genotype of rs2227981 was more frequent in AML patients and was associated with a significantly increased risk of disease by 3-fold (OR = 3.020, 95% CI: 1.265–7.209,
P
=0.013) and worse overall survival (
P
=0.271). Examination of inheritance models demonstrated significant associations in the recessive model (GG vs. AA+AG;
P
=0.011) and the over-dominant model (AG vs. AA+GG;
P
=0.011). No statistically significant differences were found between AML (with or without splenomegaly,
P
>0.05) regarding PD-1 rs2227981 genotypic distributions (AA, AG, GG), allele frequencies (A and G), and inheritance models including dominant, recessive, or over-dominant.



Conclusion
PD-1 (rs2227981) GG genotype was more frequent in AML patients, particularly under the recessive and over-dominant genetic models. These findings should be incorporated into the risk assessment model to inform and guide management for those patients.