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Notch 信号与慢性乙型肝炎病毒感染的性别特异性关联:来自台湾生物银行的研究。

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

机构信息

Institute of Public Health, National Yang Ming Chiao Tung University, Taipei, Taiwan.

Institute of Brain Science, National Yang Ming Chiao Tung University, No. 155, Sec. 2, Li-Nong St., Beitou, Taipei, 11221, Taiwan.

出版信息

Biol Sex Differ. 2024 Sep 5;15(1):69. doi: 10.1186/s13293-024-00641-z.

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.

摘要

背景

乙型肝炎是一种由乙型肝炎病毒(HBV)引起的肝脏感染,可发展为慢性感染,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 FUMA 中的基因功能分析来研究男性和女性之间 Notch 表达和加工前的反应组的差异。

方法

我们分析了 2008 年至 2019 年间从台湾生物银行(TWB)收集的 48874 名女性和 23178 名男性个体的数据。根据血液学中的乙型肝炎表面抗原(HBsAg)状态,阳性和阴性在全基因组关联研究(GWAS)分析中被分为病例和对照。

结果

我们发现了 4715 名女性和 2656 名男性 HBV 病例。男性和女性之间的基因组风险位点不同。在男性中,检测到三个风险位点(rs3732421、rs1884575 和 Affx-28516147),而在女性中则发现了八个风险位点(Affx-4564106、rs932745、rs7574865、rs34050244、rs77041685、rs107822、rs2296651 和 rs12599402)。此外,性别也呈现出不同的结果。在女性中,最显著的 SNPs 聚集在 6 号染色体上。然而,除了 6 号染色体外,男性中还可以在 3 号染色体上发现显著的乙型肝炎感染 SNPs。我们进一步在 FUMA 中研究基因功能,以确定男性和女性之间 Notch 表达和加工前的反应组的差异。我们发现,POGLUT1 和 HIST1H2BC 仅出现在男性中,而不在女性中。

结论

根据我们的研究,与女性相比,台湾男性的 Notch 表达前反应组中的 POGLUT1 和 HIST1H2BC 与乙型肝炎的风险相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6ff/11378497/ec86426032a4/13293_2024_641_Fig1_HTML.jpg

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