p53 p.Pro72Arg (rs1042522) and Mouse Double Minute 2 (MDM2) Single-Nucleotide Polymorphism (SNP) 309 Variants and Their Interaction in Chronic Lymphocytic Leukemia(CLL): A Survey in CLL Patients from Western Iran

Nazanin Jalilian; Yosra Maleki; Ebrahim Shakiba; Mozafar Aznab; Ziba Rahimi; Mehdi Salimi; Zohreh Rhimi

doi:10.18502/ijhoscr.v15i3.6846

Nazanin Jalilian Department of Clinical Biochemistry, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran
Yosra Maleki Department of Clinical Biochemistry, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran
Ebrahim Shakiba Department of Clinical Biochemistry, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran
Mozafar Aznab Department of Internal Medicine, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran
Ziba Rahimi Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
Mehdi Salimi Department of Internal Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
Zohreh Rhimi Department of Clinical Biochemistry, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran

DOI: https://doi.org/10.18502/ijhoscr.v15i3.6846

Keywords: CLL, p53, Mouse double minute 2 (MDM2), gene polymorphism, gene-gene interaction

Abstract

Background: Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults. The MDM2 and p53 are interacting proteins that play crucial roles in cell biology. Genetic variations of p53 and MDM2 have been identified in many cancers including CLL; among which are SNP309 in the promoter of MDM2 and SNP codon72 in p53.

Materials and Methods: In this study, we sought to find the impact of two SNPs of p53 and MDM2 in the pathogenesis of CLL. A total of 100 CLL patients and 102 healthy controls were recruited. Genomic DNA was extracted, and genotyping was performed using the PCR-RFLP method. The allele and genotype associations were analyzed using the χ2 test. The gene-gene interaction analysis was studied using GMDR v0.9.

Results: Our study found the absence of a signiﬁcant difference between CLL patients and controls related to the allelic frequencies or genotypic distributions for both MDM2 SNP309 and p53 codon72. A significantly higher frequency of p53 C allele was found in patients with disease duration of more than 36 compared to those less than 36 months. However, GMDR analysis suggests genetic interaction between the genes under study.

Conclusion: Our findings indicated each polymorphism of p53 codon72 and MDM2 (SNP309) was not a risk factor for CLL but the p53 C allele could be associated with the disease duration. Besides, the interaction between p53/MDM2 genotypes may confer susceptibility to CLL. Our study could be useful in genetic association studies of CLL and the role of gene-gene interactions in the susceptibility to the disease.