Association between ТР53, MDM2 and NQO1 gene polymorphisms and viral load among women with human papillomavirus.

A.H Albosale,E V Mashkina

doi:10.18699/vjgb-22-09

Abstract

The risk of cervical cancer is caused by persistent human papillomavirus (HPV) infection. Cervical cancer is the most frequent cancer among women. Our purpose was to investigate the association between TP53 215C>G (Pro72Arg), MDM2 -410T>G, and NQO1 609C>T gene polymorphisms with a high HPV load and the inf luence of gene-gene interactions on prolonged HPV infection. Eighty-nine women with a high HPV viral load and 114 healthy women were involved in a case–control study. Genotyping for TP53 215C>G (Pro72Arg) and MDM2 -410T>G SNPs was carried out by allele-specif ic PCR and genotyping for NQO1 609C>T was performed by a TaqMan assay. Quantitative analysis of HPV DNA was performed by AmpliSens® HPV HCR screen-titer-FRT test system. Gene-gene interactions were analyzed using the multifactor dimensionality reduction (MDR) method. The study of separate SNPs of MDM2 -410T>G and NQO1 609C>T genes did not reveal any statistically signif icant difference in genotype and allele frequencies among women within the two groups. The frequency of the 215G (72Arg) allele and 215GG (72Arg/ Arg) genotype of the TP53 gene was signif icantly higher in the case group than in the control group (OR = 1.74, 95 % CI = 1.10–2.73; p = 0.02 and OR = 1.97, 95 % CI = 1.13–3.46; p = 0.04, respectively). MDR analysis showed the signif icance of intergenic interactions of the three studied loci TP53 (rs1042522) – MDM2 (rs2279744) – NQO1 (rs1800566) for the formation of a high HPV load (OR = 3.05, 95 % CI = 1.73–5.46; p = 0.0001).

Highlights

Human papillomavirus (HPV) is implicated in the development of cervical cancer
Our work aims to analyze the distribution of the polymorphisms of the TP53 gene, MDM2 gene, and NQO1 gene in patients with HPV load versus HPV-negative women
The polymorphic variants of MDM2 -410T>G and NQO1 609C>T were not associated with a high HPV load

Summary

Introduction

Human papillomavirus (HPV) is implicated in the development of cervical cancer. There is heterogeneity in the development of human papillomavirus infection due to genetic variations, ethnicity, viral types involved in infection, viral load, and oncogenic expression, as well as environmental, and hormonal, phy siological, and nutritional factors (Roura et al, 2016; Tasic et al, 2018). After HPV-infection, especially with high-risk HPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59), HPV oncoproteins induce mutations in oncogenes, epigenetic modifications, and chromosomal rearrangements (Mittal, Banks, 2017). Modifications that alter the stability of cell cycle proteins such as retinoblastoma protein (pRb), tumor suppressor p53, result in uncontrolled cell cycle progression and induce oncogenic transformation of cells (Sen et al, 2017; Balasubramaniam et al, 2019)

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