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干扰素-γ诱导蛋白 10 启动子多态性与中国汉族人群乙型肝炎病毒感染疾病进展的关系。

Association of interferon-gamma induced protein 10 promoter polymorphisms with the disease progression of hepatitis B virus infection in Chinese Han population.

机构信息

Viral Hepatitis Research Laboratory, Beijing 302 Hospital, Beijing, China.

出版信息

PLoS One. 2013 Sep 4;8(9):e72799. doi: 10.1371/journal.pone.0072799. eCollection 2013.

Abstract

BACKGROUND AND AIMS

Interferon-gamma induced protein 10 (IP-10) was suggested to be involved in liver injury in viral hepatitis. This study aimed to investigate the impact of the single nucleotide polymorphisms (SNP) G-201A (rs1439490) in IP-10 gene on disease progression of hepatitis B virus (HBV) infection.

METHODS

The -201 SNP in IP-10 promoter was genotyped from 577 patients with different illness categories and 275 health controls; In vitro IP-10 promoter activity was compared between haplotype GG and AA homozygotes using luciferase reporter system in HepG2 cells. In vivo expression of IP-10 was compared between patients with -201 AA genotype and GG genotype.

RESULTS

The detected frequency of G-201A SNP was 17.8%, 25.3%, 26.6%, and 13.8% for patients with acute hepatitis B (AHB), patients with mild chronic hepatitis B (CHB-M), patients with severe chronic hepatitis B (CHB-S), and health controls, respectively. In vitro IP-10 promoter-driven luciferase activity in pGL3-Enhancer-201A transfected HepG2 cells was 1.43-fold higher than that in pGL3-Enhancer-201G transfected HepG2 cells (P<0.01). In vivo IP-10 transcriptional expression of peripheral blood mononuclear cells was 1.38-fold higher in patients with -201 AA genotype than in patients with -201 GG genotype (P<0.01).

CONCLUSION

G-201A in promoter region of IP-10 gene was associated with liver disease progression in patients with HBV infection through up-regulating IP-10 expression.

摘要

背景与目的

干扰素-γ诱导蛋白 10(IP-10)被认为参与了病毒性肝炎中的肝损伤。本研究旨在探讨 IP-10 基因中单个核苷酸多态性(SNP)G-201A(rs1439490)对乙型肝炎病毒(HBV)感染疾病进展的影响。

方法

从不同疾病类别的 577 名患者和 275 名健康对照中检测 IP-10 启动子中的-201 SNP;在 HepG2 细胞中使用荧光素酶报告系统比较单倍型 GG 和 AA 纯合子之间的 IP-10 启动子活性;比较-201AA 基因型和 GG 基因型患者体内 IP-10 的表达。

结果

急性乙型肝炎(AHB)、轻度慢性乙型肝炎(CHB-M)、重度慢性乙型肝炎(CHB-S)和健康对照组患者中 G-201A SNP 的检出频率分别为 17.8%、25.3%、26.6%和 13.8%。与 pGL3-Enhancer-201G 转染 HepG2 细胞相比,pGL3-Enhancer-201A 转染 HepG2 细胞中的 IP-10 启动子驱动的荧光素酶活性高 1.43 倍(P<0.01)。-201AA 基因型患者外周血单个核细胞中 IP-10 的转录表达比-201GG 基因型患者高 1.38 倍(P<0.01)。

结论

IP-10 基因启动子区域的 G-201A 与 HBV 感染患者的肝病进展有关,通过上调 IP-10 表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60a0/3762918/9dea29d487e9/pone.0072799.g001.jpg

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