Sex-specific associations of Notch signaling with chronic HBV infection: a study from Taiwan Biobank.

ABSTRACT

BACKGROUND: Hepatitis B, a liver infection caused by the hepatitis B virus (HBV), can develop into a chronic infection that puts patients at high risk of death from cirrhosis and liver cancer. In this study, we aimed to investigate the difference of reactome pre-Notch expression and processing between males and females by using gene to function analysis in FUMA. METHODS: We analyzed Taiwan Biobank (TWB) data pertaining to 48,874 women and 23,178 men individuals which were collected from 2008 to 2019. According to hepatitis B surface antigen (HBsAg) status in hematology, positive and negative were classified into case and control in the genome-wide association study (GWAS) analysis. RESULTS: We found 4715 women and 2656 men HBV cases. The genomic risk loci were different between males and females. In male, three risk loci (rs3732421, rs1884575 and Affx-28516147) were detected while eight risk loci (Affx-4564106, rs932745, rs7574865, rs34050244, rs77041685, rs107822, rs2296651 and rs12599402) were found in female. In addition, sex also presented different results. In females, the most significant SNPs are gathered in chromosome 6. However, except for chromosome 6, significant HBV infection SNPs also could be found in chromosome 3 among males. We further investigated gene function in FUMA to identify the difference in reactome pre-Notch expression and processing between males and females. We found that POGLUT1 and HIST1H2BC only appeared in men but not in women. CONCLUSION: According to our study, the reactome pre-Notch expression including POGLUT1 and HIST1H2BC was associated with a risk of Hepatitis B in Taiwanese men when compared to women.

Hepatitis B is a serious liver infection caused by the hepatitis B virus (HBV). It can lead to long-term liver damage and cancer. We looked at differences in how the virus affects men and women in Taiwan. We analyzed data from over 72,000 people in the Taiwan Biobank. The study individuals were divided into two groups­those who had the hepatitis B virus (cases) and those who did not (controls). We looked for genetic differences between the two groups and found that the specific genetic risk factors for hepatitis B differed between men and women. We found three genetic risk factors in men and eight in women. This suggests that the way the hepatitis B virus interacts with our genes may differ between the sexes. We found that in women, the most significant genetic risk factors were all located on chromosome 6. However, in men, the significant risk factors were spread across different chromosomes, including chromosome 3. Finally, we looked at how these genetic differences might affect the way the body processes the hepatitis B virus. We found that two specific genes, called POGLUT1 and HIST1H2BC, were only linked to hepatitis B risk in men, not in women. This indicates that the biological pathways involved in hepatitis B infection may differ between males and females. Understanding these differences could lead to more effective, personalized treatment strategies for those affected by the virus.