TP53 Gene 72 Arg/Pro (rs1042522) Single Nucleotide Polymorphism Contribute to Increase the Risk of B-Chronic Lymphocytic Leukemia in the Sudanese Population

Abstract

Objective: This study aimed at exploring the association of TP53 72Arg/Pro polymorphism and Risk of Chronic<br />Lymphocytic Leukemia and to assess the correlation between TP53 72Arg/Pro polymorphism and clinical parameter,<br />hematological profile and some biological prognostic markers among Sudanese patients with chronic lymphocytic<br />leukemia. Methods: A case-control study was conducted in Khartoum state, Sudan, during the period from April 2017 to<br />April 2018, involved 110 B-CLL patients and 80 healthy volunteers as a control group. Physical examination, Complete<br />Blood Count and Immunophenotype were performed in all patients to confirm the diagnosis. Clinical staging such as<br />Rai and Binet were studied. CD38 and ZAP70 were performed by Flow Cytometry. Blood samples were collected from<br />all participants; DNA was extracted by using ANALYTIKJENA Blood DNA Extraction Kit (Germany) and analyzed<br />TP53 codon 72Arg/Pro Polymorphism by using AS-PCR. The statistical analysis was performed using SPSS version<br />23.0 software (Chicago, IL, USA). Results: the Arg/Pro was the most frequent genotype in B-CLL patients(50%),<br />followed by Arg/Arg (25.5%) and Pro/Pro (24.5%), whereas in healthy control group Arg/Pro was the most frequent<br />(47.5%), followed by Arg/Arg (45%) and Pro/Pro (7.5%). Our data indicate a higher frequency of homozygous Pro/<br />Pro in the B-CLL patients as compared to controls with an OR of 4.01 for the Pro/Pro genotype and lower frequency<br />of Arg/Arg genotype in CLL patients as compared to controls with an OR of .42 for the Arg/Arg genotype. Also, the<br />Pro allele showed higher risk than Arg allele (P value=0.000, OR 2.23, 95% CI=1.45-3.41). No significant association<br />between gender, clinical staging systems (Rai, Binet), biological prognostic markers (CD38 expression or ZAP70<br />expression), and TP53 codon 72Arg/Pro polymorphisms, except Arg/Arg genotype tended to be associated with younger<br />age (P =0.04). Conclusion: Our data suggested that Pro/Pro genotype contribute to increased susceptibility to B-Chronic<br />Lymphocytic Leukemia risk in our population tenfold higher than those had Arg/Arg genotype