GAS5 rs2067079 and miR-137 rs1625579 functional SNPs and risk of chronic hepatitis B virus infection among Egyptian patients

Rania H Mahmoud,Olfat G Shaker,Omayma O Abdelaleem,Amal A Ibrahim,Doaa Y Ali,Noha K Abdelghaffar,Enas Mamdouh Hefzy,Mohamed M Mohamed,Tarek I Ahmed,Essam A Hassan

doi:10.1038/s41598-021-99345-2

Rania H Mahmoud, Olfat G Shaker + Show 8 more

Open Access

https://doi.org/10.1038/s41598-021-99345-2

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Journal: Scientific Reports	Publication Date: Oct 8, 2021
Citations: 2	License type: open-access

Affiliation: Fayoum University, Cairo University

Abstract

Hepatitis B virus (HBV) infection is a significant health issue worldwide.. We attempted to fulfill the molecular mechanisms of epigenetic and genetic factors associated with chronic HBV (CHBV). Expression levels of the lncRNA growth arrest-specific 5 (GAS5) and miR-137 and their corresponding SNPs, rs2067079 (C/T) and rs1625579 (G/T) were analyzed in 117 CHBV patients and 120 controls to investigate the probable association between these biomarkers and CHBV pathogenesis in the Egyptian population. Serum expression levels of GAS5 and miR-137 were significantly down-regulated in cases vs controls. Regarding GAS5 (rs2067079), the mutant TT genotype showed an increased risk of CHBV (p < 0.001), while the dominant CC was a protective factor (p = 0.004). Regarding miR-137 rs1625579, the mutant genotype TT was reported as a risk factor for CHBV (p < 0.001) and the normal GG genotype was a protective factor, p < 0.001. The serum GAS5 was significantly higher in the mutant TT genotype of GAS5 SNP as compared to the other genotypes (p = 0.007). Concerning miR-137 rs1625579, the mutant TT genotype was significantly associated with a lower serum expression level of miR-137 (p = 0.018). We revealed the dysregulated expression levels of GAS5 and miR-137 linked to their functioning SNPs were associated with CHBV risk and might act as potential therapeutic targets.

Highlights

Hepatitis B virus (HBV), a double-stranded DNA virus, is a member of the Hepadnavirus family
In chronic HBV (CHBV) patients, the serum expression level of growth arrest-specific 5 (GAS5) and miR-137 was significantly down-regulated in cases vs controls, p < 0.001 for each (Table 1 and Fig. 1)
We have explored the influence of the expression levels of GAS5 and its rs2067079 SNP and miR-137 and its rs1625579 SNP on CHBV susceptibility, and we have demonstrated them as potential genetic biomarkers

Summary

Introduction

Hepatitis B virus (HBV), a double-stranded DNA virus, is a member of the Hepadnavirus family. HBV infection leads to hepatic acute and chronic diseases. HBV infection causes the development of various liver diseases including hepatocellular carcinoma (HCC), cirrhosis, acute and chronic h epatitis[1]. Noncoding RNAs (ncRNAs) are defined as RNAs possessing the little capability of protein‐coding They function as promising regulators of epigenetic, transcriptional, and post-transcriptional gene expression. Studies reported that the lncRNA growth arrest-specific 5 (GAS5) is needed for arrest of normal growth, and slowing of the cell cycle[8]. It has diverse functions in regulating gene expression, induction of cell apoptosis, suppression of tumorigenesis[9], and inhibition of T-cell p roliferation[10]. Little is known about the role of miR-137 in chronic liver diseases

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