Association between Hypoxia-inducible Factor-1α gene polymorphisms and risk of chronic hepatitis b and hepatitis b virus-related liver cirrhosis in a Chinese population: A retrospective case–control study

Yu, Lu; Sui, Jingzhe; Liu, Yanqiong; Li, Ruolin; Ma, Liping; Zhang, Xiaolian; Qin, Xue; Li, Shan

doi:10.1016/j.gene.2015.03.053

Cited by 8 publications

(4 citation statements)

References 43 publications

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“…Furthermore, haplotype analysis indicated that the GG haplotype might be a protective factor for LC in the Guangxi population. According to our latest studies [ 33 , 45 ] on the association between HIF-1a genetic polymorphisms (rs11549465 and rs115494657) and the risk of HBV-related liver disease, we did not find an association between HIF-1a rs11549465 and rs11549467 polymorphisms and HBV-related liver disease. However, the HIF-1a CG and CA haplotypes might be a risk factor and a protective marker, respectively, for HBV-related HCC in the Guangxi population.…”

Section: Discussioncontrasting

confidence: 72%

Association of Hypoxia-Inducible Factor-2 Alpha Gene Polymorphisms with the Risk of Hepatitis B Virus-Related Liver Disease in Guangxi Chinese: A Case-Control Study

et al. 2016

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ObjectiveHypoxia-inducible factor-2 alpha (HIF-2a) plays a major role in the progression of disease, although the role of HIF-2α gene polymorphisms in hepatitis B virus (HBV)-related diseases remains elusive. The aim of this study is to determine whether HIF-2a rs13419896 and rs6715787 single-nucleotide polymorphisms (SNPs) are associated with susceptibility to chronic hepatitis B (CHB), liver cirrhosis (LC), or hepatocellular carcinoma (HCC).MethodA case-control study of 107 patients with CHB, 83 patients with LC, 234 patients with HCC, and 224 healthy control subjects was carried out, and the HIF-2a rs13419896 and rs6715787 SNPs were genotyped by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP).ResultsNo significant differences were observed in the genotype or allele frequency of two HIF-2a SNPs between the cases and controls (all p>0.05). However, in subgroup analysis by gender, the HIF-2a rs13419896 GA and AA genotypes were significantly associated with a risk of CHB (odds ratio [OR] = 3.565, 95% confidence interval [CI] = 1.123–11.314, p = 0.031 and OR = 12.506, 95% CI = 1.329–117.716, p = 0.027) in females, and the A allele of rs13419896 was associated with a risk of CHB (OR = 2.624, 95% CI = 1.244–5.537, p = 0.011) and LC (OR = 2.351, 95% CI = 1.002–5.518, p = 0.050) in females. The rs6715787 CG genotype polymorphism may contribute to a reduced risk of LC in the Guangxi Zhuang Chinese population (OR = 0.152, 95% CI = 0.028–0.807, p = 0.027), as determined via subgroup analysis by ethnicity. Moreover, binary logistic regression analyses that were adjusted by drinking status indicated that the AA genotype of rs13419896 may contribute to an increased risk of LC in the non-alcohol-drinking population (OR = 3.124, 95% CI = 1.091–8.947, p = 0.034). In haplotype analysis, GG haplotype was significantly associated with a reduced risk of LC (OR = 0.601, 95% CI = 0.419–0.862, p = 0.005).ConclusionsThe HIF-2a rs13419896 polymorphism is associated with an increased risk of CHB and LC in the Guangxi Chinese population, especially in females and in the non-alcohol-drinking population, while the HIF-2a gene rs6715787 polymorphism is associated with a decreased risk of LC in the Guangxi Zhuang population.

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Section: Discussioncontrasting

confidence: 72%

Association of Hypoxia-Inducible Factor-2 Alpha Gene Polymorphisms with the Risk of Hepatitis B Virus-Related Liver Disease in Guangxi Chinese: A Case-Control Study

et al. 2016

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“…6 However, the factors that affect the development of cirrhosis and/or HCC in HBV carriers are poorly understood. 7 Helicobacter pylori infects over 50% of the human population and usually colonizes the gastric mucosa. 8 In 1994, the World Health Organization recognized H. pylori as a group 1 carcinogen contributing to gastric cancer.…”

mentioning

confidence: 99%

Helicobacter pylori infection may increase the risk of progression of chronic hepatitis B disease among the Chinese population: a meta-analysis

Wang

Chen

Zheng

et al. 2016

International Journal of Infectious Diseases

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“…Maintenance appropriate oxygen and angiogenic factors are essential for HCC growth. HIF-1α has been implicated in regulating hepatic in ammatory progression, and associated with multiple in ammationrelated cancers or signaling pathway activation of HBV-related HCC [20,21] . The presence of hypoxia in tissues restricts HCC overgrowth because of HIF-1α regulating cellular metabolism, immune escape, angiogenesis, metastasis [22] , extracellular matrix remodeling, cancer stem cells (CSC) [23,24] or MDR via regulating PI3K/AKT/HIF-1α/MDR-1 pathway [25,26] .…”

Section: Discussionmentioning

confidence: 99%

HIF-1α promotes hepatocellular carcinoma metastasis by regulating angiogenesis and epithelial-mesenchymal transition

Yao

Wang

Chen

et al. 2020

Preprint

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Background Invasion and metastasis of hepatocellular carcinoma (HCC) still remain to be hard in medical society. However, little knowledge is known regarding the hypoxia impact in HCC with angiogenesis and epithelial-mesenchymal transition (EMT). The aims of this study were to explore the regulating roles of hypoxia-inducible factor-1α (HIF-1α) in angiogenesis and EMT of HCC. Methods The levels of HIF-1α, angiopoietin-2 (Ang-2), and vascular endothelial growth factor (VEGF) expression in a cohort of chronic liver diseases were detected by enzyme-linked immunosorbent assays, and their dynamic up-regulations were confirmed in model of rat hepatocyte malignant transformation. After HIF-1α gene transfected with specific miRNA, biological behaviors of HCC cells were analyzed by transwell or invasion assay; angiogenesis and EMT were analyzed at protein level by Western blot or at mRNA by quantitative real-time PCR. Results The levels of circulating HIF-1α, VEGF, and Ang-2 in the HCC group (145.6 ± 32.6 µg/L, 458.9 ± 125.3 µg/L, and 42.9 ± 5.1 µg/L) were significantly higher (P < 0.001) than those in the LC (79.5 ± 8.4 µg/L, 206.8 ± 56.8 µg/L, and 26.2 ± 6.1 µg/L) or the CH (60.1 ± 18.8 µg/L, 178.1 ± 85.4 µg/L, and 21.8 ± 6.9 µg/L) group, respectively. Dynamic up-regulations of HIF-1α and angiogenic factors have been confirmed by rat model with hepatocyte malignant transformation. There were closely positive correlations (P < 0.001) between them of HIF-1α and VEGF or Ang-2. After HCC cells transfected with specific HIF-1α-miRNA, the levels of HIF-1α, VEGF and Ang-2 expression were significantly down-regulated, with inhibiting infiltration or migration, blockading EMT with increasing E-cadherin and decreasing of snail, twist and vimentin. Conclusions These data have highlighted the HIF-1α over-expression could promote the metastasis or invasion of HCC via regulating neovascularization and EMT formation.

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Association between Hypoxia-inducible Factor-1α gene polymorphisms and risk of chronic hepatitis b and hepatitis b virus-related liver cirrhosis in a Chinese population: A retrospective case–control study

Cited by 8 publications

References 43 publications

Association of Hypoxia-Inducible Factor-2 Alpha Gene Polymorphisms with the Risk of Hepatitis B Virus-Related Liver Disease in Guangxi Chinese: A Case-Control Study

Association of Hypoxia-Inducible Factor-2 Alpha Gene Polymorphisms with the Risk of Hepatitis B Virus-Related Liver Disease in Guangxi Chinese: A Case-Control Study

Helicobacter pylori infection may increase the risk of progression of chronic hepatitis B disease among the Chinese population: a meta-analysis

HIF-1α promotes hepatocellular carcinoma metastasis by regulating angiogenesis and epithelial-mesenchymal transition

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