背景:乙型肝炎,由乙型肝炎病毒(HBV)引起的肝脏感染,会发展成慢性感染,使患者面临肝硬化和肝癌死亡的高风险。在这项研究中,我们旨在通过对FUMA进行基因功能分析,研究男性和女性之间反应小体pre-Notch表达和加工的差异。
方法:我们分析了2008年至2019年收集的48,874名女性和23,178名男性的台湾生物库(TWB)数据。根据乙型肝炎表面抗原(HBsAg)在血液学状态,在全基因组关联研究(GWAS)分析中将阳性和阴性分为病例和对照.
结果:我们发现4715名女性和2656名男性HBV病例。男性和女性的基因组风险位点不同。在男性中,在女性中检测到三个风险位点(rs3732421,rs1884575和Affx-28516147),而八个风险位点(Affx-4564106,rs932745,rs7574865,rs34050244,rs77041685,rs107822,rs2296651和rs12599402)。此外,性别也呈现不同的结果。在女性中,最重要的SNP聚集在6号染色体上。然而,除6号染色体外,男性的3号染色体也有显著的HBV感染SNP。我们进一步研究了FUMA中的基因功能,以确定男性和女性之间反应小体pre-Notch表达和加工的差异。我们发现POGLUT1和HIST1H2BC仅出现在男性中,而不出现在女性中。
结论:根据我们的研究,与女性相比,在台湾男性中,包括POGLUT1和HIST1H2BC在内的反应性pre-Notch表达与乙型肝炎风险相关.
乙型肝炎是由乙型肝炎病毒(HBV)引起的严重肝脏感染。它可以导致长期的肝损伤和癌症。我们研究了该病毒如何影响台湾男性和女性的差异。我们分析了台湾生物库72,000多人的数据。研究人员分为两组-那些有乙型肝炎病毒(病例)和那些没有(对照)。我们寻找两组之间的遗传差异,发现乙型肝炎的特定遗传风险因素在男性和女性之间有所不同。我们发现男性有三个遗传风险因素,女性有八个。这表明乙型肝炎病毒与我们的基因相互作用的方式可能在性别之间有所不同。我们发现在女性中,最显著的遗传危险因素均位于6号染色体上。然而,在男人中,显著的危险因素分布在不同的染色体上,包括3号染色体.最后,我们研究了这些遗传差异如何影响身体处理乙型肝炎病毒的方式。我们发现两个特定的基因,称为POGLUT1和HIST1H2BC,只与男性的乙型肝炎风险有关,不是女人。这表明乙型肝炎感染的生物学途径可能在男性和女性之间有所不同。了解这些差异可能会导致更有效的,针对受病毒影响的患者的个性化治疗策略。
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.
CONCLUSIONS: 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 groups—those 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.