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Abstract

DNA METHYLATION PATTERN OF L1 GENE OF HIGH RISK HUMAN PAPILLOMAVIRUSES AND IFN-GAMMA AS A CANDIDATE BIOMARKERS FOR PREDISPOSE TO CERVICAL NEOPLASIA IN WOMEN FROM BAGHDAD

Hiba Sabah Jasim and Maysaa Abdul Razzaq Dhahi*

ABSTRACT

Background: Human papillomaviruses (HPV) are the etiological agents of cervical malignancies. DNA Methylation of late genes (L1) of high risk human papilloma viruses genotypes (HR- HPVs) takes place regularly in cervical cells and its elevated in high grade lesions and cancer cases when compared to asymptomatic infection or lowgrade lesions. Interferons gama(IFN-γ) are antiviral molecules that induce a state of resistance to viral replication in infected and uninfected neighbor cells and regulate the cellular immune response. Methods: Fresh cervical tissue biopsy samples were collected from hysterectomy done for women. Extracted DNA from these samples were subjected to amplification using PCR to estimate DNA integrity, viral DNA identification, genotyping of HR-HPVs, sodium bisulfite modification and study of DNA methylation pattern of L1 gene and IFN-γ gene. Results: From totally collected 150 samples,90 samples were subjected to all study tests. From them, 24/90 were included in the study of DNA methylation pattern of viral L1 gene; 14/90 samples as control group and 10/90 samples as patient groups whom positive for HPV-16,18 and/or 45. Positivity for DNA methylation of L1 gene was 100% in samples positive to HPV-18 and HPV-45, while it was 66.7%. in samples positive to HPV-16.DNA methylation state of IFN-gamma was detected in patients group as 10/10(100%), while the positivity of the DNA methylation of IFN-gamma in the control group was 4/14(28.6%). Conclusion: Methylation of L1 gene and IFN-γ gene has a role as a candidate biomarker for the progression of cervical disease.

Keywords: Human Papilloma Virus, DNA methylation, L1 gene, IFN-gamma, risk factor.


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