Association of codon 72 polymorphism of p53 with the severity of cervical dysplasia, E6-T350G and HPV16 variant lineages in HPV16-infected women.
Moschonas George D,Tsakogiannis Dimitris,Lamprou Konstantinos A,Mastora Eirini,Dimitriou Tilemachos G,Kyriakopoulou Zaharoula,Kottaridi Christine,Karakitsos Petros,Markoulatos Panayotis
Journal of medical microbiology
Polymorphic variability in the tumour-suppressor protein p53 at codon 72 has a considerable impact on cervical cancer development. The present study clarified the association between p53 codon 72 genotypes and the risk of cervical disease in Greek patients. We also examined whether the presence of specific p53 genotypes in combination with HPV16 variants or E6 T350G sequence variation can modify an individual's susceptibility to cervical disease. The analysis of p53 genotypes was performed through PCR-RFLP. Sequence and phylogenetic tree analyses of the HPV16 E6 gene were also performed in order to identify HPV16 variants and T350G sequence variation. The outcomes of the present analysis revealed that women who are homozygous for the arg genotype are at a 4.17-fold higher risk of developing HPV16-associated HSIL+ (OR=4.17, 95 % CI:1.48-4.9, =0.0049). Moreover, p53 arg/arg patients infected by an HPV16 prototype strain were associated with an increased risk of more severe lesions, while a significant relationship between the p53 arg/arg genotype in patients with T350G sequence variation and the risk of high-grade squamous intraepithelial lesions (HSILs) was revealed. The oncogenic potential of the virus is increased by the presence of the p53 arg/arg genotype in the Greek population in such a way that the specific protein interaction E6 (L83V)-p53 (Arg-72) can modify an individual's susceptibility to cervical disease.
Association between the p53 arginine/arginine homozygous genotype at codon 72 and human papillomavirus E6/E7 mRNA expression.
Chuery Ana Carolina Silva,Silva Ismael Dale Cotrim Guerreiro da,Ribalta Julisa Chamorro Lascasas,Speck Neila Maria de Góis
The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases
OBJECTIVE:To evaluate the association between p53 polymorphisms and human papillomavirus (HPV) E6/E7 mRNA expression. METHODS:We analyzed 175 cervical samples from women aged 16-69 years old who were tested for HPV E6/E7 mRNA expression (NucliSENS EasyQ HPV). The samples were divided into three groups: positive (n=75) those with positive HPV E6/E7 mRNA expression and positive high-risk HPV Hybrid Capture (HR-HC) test; negative (n=52) those with negative HPV E6/E7 mRNA expression and positive HR-HC; and control (n=48) those with negative HPV E6/E7 mRNA expression and negative HR-HC. The p53 polymorphisms at codons 11, 72, and 248 were evaluated through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS:The frequency of the arginine/arginine homozygous genotype at codon 72 was significantly higher in the positive (49.3%) than in the negative (32.7%) and control groups (20.8%, p=0.002*). The frequency of the arginine allele was also significantly higher in the positive (67.3%) than in the negative (53.8%) and control groups (38.5%, p<0.001*). The arginine/arginine homozygous genotype was significantly associated with positive HPV E6/E7 mRNA expression (positive group) compared with negative and control groups (odds ratio: 2.633; 95% CI, 1.399-4.954, p=0.003). The frequency of arginine/arginine homozygous genotype at codon 72 remained significantly more frequent in the positive group of women aged ≥30 years than in the other two groups. CONCLUSION:The presence of the p53 arginine/arginine homozygous genotype at codon 72 was significantly associated with the positive HPV E6/E7 mRNA expression.