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

Ameen Abdulaziz Mohammed Basabaeen,Enaam Abdalrhman Abdelgader,Ebtihal Ahmed Babekir,Eman Abbass Fadul,Abdulwali Sabo,Saadia Osman Abdelrahim,Osama Ali Altayeb,Ibrahim Khider Ibrahim,Nada Hassan Eltayeb

doi:10.31557/apjcp.2019.20.5.1579

Abstract

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

Highlights

B cell chronic lymphocytic leukemia (CLL) is the most common type of leukemia in adults in Western countries, and mainly affects elderly individuals (Chiorazzi et al, 2005)
Our data indicate a higher frequency of homozygous Pro/ Pro in the B-CLL patients as compared to controls with an odds ratio (OR) of 4.01 for the Pro/Pro genotype and lower frequency of Arg/Arg genotype in CLL patients as compared to controls with an OR of .42 for the Arg/Arg genotype
CLL heterogeneity may be associated with single nucleotide polymorphic (SNP) variation

Summary

Introduction

B cell chronic lymphocytic leukemia (CLL) is the most common type of leukemia in adults in Western countries, and mainly affects elderly individuals (Chiorazzi et al, 2005). The TP53 codon 72 polymorphism is located in exon 4 with CGC to CCC transition, leading to an Arginine-to-Proline amino acid substitution in amino acid position 72 (Whibley et al, 2009) These SNP appear to be different both biochemically and biologically (Thomas et al, 1999; Dumont et al, 2003; Pim and Banks, 2004).The laboratory studies demonstrated that Arg variant is more potent in apoptosis induction whereas the Pro variant is better in inducing cell cycle arrest and DNA damage repair (Dumont et al, 2003; Pim and Banks, 2004; Siddique and Sabapathy, 2006). Recent study shown that the Proline allele in the homozygous state was associated with a shorter time to the first treatment among the group of patients with mutated IGHV locus (Majid et al, 2011)

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