Determination of P53 gene polymorphisms in patients with myelodysplastic syndrome and introducing their correlation with disease

Myelodysplastic syndrome (MDS) is a clonal disease with reduced hematopoiesis and elevated apoptosis and increased risk of acute myeloid leukemia (AML) conversion. The pathogenesis of MDS has not been fully elucidated. Approximately 50% of patients have a karyotype abnormality and this ratio is increased to 80% in the secondary MDS. P53 is a key regulator of stem cell homeostasis that impacts an array of cellular functions including genomic surveillance, cell-cycle regulation and apoptotic and inflammatory response. Since P53 is involved in the maintenance of genomic integrity, it is one of the most frequently genetically altered genes in various cancer types. In our study, to investigate the effect of p53 single nucleotide polymorphisms (SNPs) on abnormal differentiation of MDS, we examined 4 common polymorphisms (rs35163653, rs35993958, rs1800371, rs1042522) of p53 gene in 100 patients diagnosed with MDS. After DNA extraction from blood samples of MDS cases, PCR analysis was performed via melting curve analysis for each p53 polimorphism. The results were evaluated using LightCycler software and IBM SPSS Statistics ver 25.0. Among the 4 polymorphisms studied, a significant change was found in the study group in rs1042522 C/G (R72P) convertion polymorphism. In our study, we found that non-ancestral allele is higher for rs1042522 polymorphism (C:0,303 G:0,697). rs1042522 polymorphism is associated with hematologic cancers in some studies; similar to previous findings, our data shows that this polymorphism is associated with MDS. Our allele frequency results are consistent with HapMap allele database for Caucasians population. Genome-wide association studies have shown linkage SNPs that alter p53 function and select malignancies. One of the most well-studied nonsynonymous SNPs, rs1042522 (R72P), located within codon 72 has been implicated in susceptibility and predisposition to solid tumors. Thus, we investigated its effect upon hematological disorders and concluded that people with the rs1042522 polymorphism are at increased risk of MDS. Our study is the first one in the literature showing the impact of rs1042522 polymorphism in the MDS patient group in Turkey. We may suggest that rs1042522 polymorphism can be used as a marker to diagnose MDS in the future with clinical correlations.