scholarly journals The TNFRSF13B rs34562254 Polymorphism is Associated with Hepatitis C Infection Risk in the Han Chinese Population

2021 ◽  
Author(s):  
Haozhi Fan ◽  
Zuqiang Fu ◽  
Zhijun Ge ◽  
Chen Dong ◽  
Chunhui Wang ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Tumor Necrosis Factor ◽  
Chinese Population ◽  
Tumor Necrosis ◽  
Blood Donors ◽  
Bioinformatics Analysis ◽  
Hcv Infection ◽  
Wild Type ◽  
Han Chinese Population ◽  
Necrosis Factor

Abstract Background Genetic variations in the tumor necrosis factor receptor superfamily (TNFRSF) 13B have been reported to be associated with immune-related diseases. This study aimed to explore the relationship of tumor necrosis factor superfamily (TNFSF) 13, TNFRSF13B, and TNFRSF14 missense mutations with hepatitis C virus (HCV) infection susceptibility. Methods Single-nucleotide polymorphisms (SNPs) in TNFSF13 (rs3803800, rs11552708), TNFRSF13B (rs34562254), and TNFRSF14 (rs4870) were genotyped in 469 intravenous drug users, 728 hemodialysis patients, and 1636 paid blood donors using a TaqMan real-time PCR assay. The USCS browser and RNAfold web servers were used to predict the biological functions of these selected SNPs. Results After adjusting for gender, age, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and route of infection, a logistic regression analysis showed that subjects carrying a homozygous TNFRSF13B rs34562254 TT mutant were more likely to be infected by HCV compared to those homozygous with the rs34562254 CC wild type (co-dominant model: OR = 1.52, 95% CI: 1.17–1.98, P = 0.002; recession model: OR = 1.41, 95% CI: 1.10–1.81, P = 0.007; additive model: OR = 1.21, 95% CI: 1.07–1.37, P = 0.002). The effect of the risk allele rs34562254-T was stronger in subjects that were female, older (≥ 50 years old), paid blood donors, and with lower ALT and AST levels (≤ 40 U/L). A bioinformatics analysis via the UCSC genome browser found that rs34562254 was located at the highest peak of the H3K4Me1 histone marker. Using the RNAfold web servers, the minimum free energy of the centroid secondary structure was found to be higher for the mutant rs34562254-T allele (-38.90 kcal/mol) than its wild type C allele (-45.60 kcal/mol). Additionally, the RegulomeDB score of rs34562254 was 3a. Altogether, the results of the bioinformatics analysis indicate that rs34562254 may affect gene expression levels by regulating the transcriptional activity of corresponding gene regions. Conclusions The rs34562254 polymorphisms in TNFRSF13B were significantly associated with HCV infection among the Han Chinese population.

scholarly journals Polymorphism Rs34562254 In TNFRSF13B is Associated with HCV Infection Outcomes Among Chinese Han Population

2021 ◽  
Author(s):  
Haozhi Fan ◽  
Zuqiang Fu ◽  
Zhijun Ge ◽  
Chen Dong ◽  
Chunhui Wang ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Blood Donors ◽  
Bioinformatics Analysis ◽  
Hcv Infection ◽  
Chinese Han Population ◽  
Web Servers ◽  
Chinese Han ◽  
Han Population ◽  
Necrosis Factor

Abstract Genetic variations in tumor necrosis factor receptor superfamily (TNFRSF) 13B have already proved to be associated with immune- related diseases. This study aimed to explore the relationship of tumor necrosis factor superfamily (TNFSF) 13, TNFRSF13B, and TNFRSF14 missense mutations with the susceptibility of HCV infection. SNPs in TNFSF13 (rs3803800, rs11552708), TNFRSF13B (rs34562254), and TNFRSF14 (rs4870) were genotyped in 469 intravenous drug users, 728 hemodialysis patients and 1636 paid blood donors by TaqMan real-time PCR assay. And the USCS Brower and RNAfold web servers were used to predict the potential biological functions of the positive SNPs. After adjustment for gender, age, ALT level, AST level and route of infection, the results of logistic regression analysis showed that the subjects carried rs34562254 TT mutant homozygous type in TNFRSF13B were more likely to be infected by HCV compared to those with rs34562254 CC wild homozygous type (co-dominant model: OR = 1.52, 95% CI: 1.17–1.98, P = 0.002; recession model: OR = 1.41, 95% CI: 1.10–1.81, P = 0.007; additive model: OR = 1.21, 95% CI: 1.07–1.37, P = 0.002). And the effect of the risk allele (rs34562254-T) is more evident in female, elder (≥ 50), paid blood donors, lower ALT level (≤ 40 U/L) and lower ALT level (≤ 40 U/L) subgroup. The result of bioinformatics analysis showed that rs34562254 was located at the highest peak of the H3K4Me1 histone marker with the UCSC genome browser. And the minimum free energy (MFE) of the centroid secondary structure for the mutant T allele (-38.90 kcal/mol) of rs34562254 was higher than that of the wild C allele (-45.60 kcal/mol) with the RNAfold web servers. In addition, the RegulomeDB score of rs34562254 was 3a with the RegulomeDB web servers. All the above results of bioinformatics analysis suggested that rs34562254 may affect the gene expression level by regulating the transcriptional activity of the corresponding gene region. The rs34562254 polymorphisms in TNFRSF13B were significantly associated with HCV infection among Chinese Han population.

Contributions of angiotensin II and tumor necrosis factor-α to the development of renal fibrosis

2001 ◽  
Vol 280 (5) ◽  
pp. F777-F785 ◽  
Author(s):  
Guangjie Guo ◽  
Jeremiah Morrissey ◽  
Ruth McCracken ◽  
Timothy Tolley ◽  
Helen Liapis ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Tumor Necrosis Factor ◽  
Renal Fibrosis ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Wild Type ◽  
Tnf Α ◽  
Factor Α ◽  
Tgf Β1 ◽  
Necrosis Factor

Angiotensin II upregulates tumor necrosis factor-α (TNF-α) in the rat kidney with unilateral ureteral obstruction (UUO). In a mouse model of UUO, we found that tubulointerstitial fibrosis is blunted when the TNF-α receptor, TNFR1, is functionally knocked out. In this study, we used mutant mice with UUO in which the angiotensin II receptor AT1a or the TNF-α receptors TNFR1 and TNFR2 were knocked out to elucidate interactions between the two systems. The contribution of both systems to renal fibrosis was assessed by treating TNFR1/TNFR2-double knockout (KO) mice with an angiotensin-converting enzyme inhibitor, enalapril. The increased interstitial volume (Vvint) in the C57BI/6 wild-type mouse was decreased in the AT1a KO from 32.8 ± 4.0 to 21.0 ± 3.7% ( P < 0.005) or in the TNFR1/TNFR2 KO to 22.3 ± 2.1% ( P < 0.005). The Vvint of the TNFR1/TNFR2 KO was further decreased to 15.2 ± 3.7% ( P < 0.01) by enalapril compared with no treatment. The induction of TNF-α mRNA and transforming growth factor-β1 (TGF-β1) mRNA in the kidney with UUO was significantly blunted in the AT1a or TNFR1/TNFR2 KO mice compared with the wild-type mice. Treatment of the TNFR1/TNFR2 KO mouse with enalapril reduced both TNF-α and TGF-β1 mRNA and their proteins to near normal levels. Also, α-smooth muscle actin expression and myofibroblast proliferation were significantly inhibited in the AT1a or TNFR1/TNFR2 KO mice, and they were further inhibited in enalapril-treated TNFR1/TNFR2 KO mice. Incapacitating the angiotensin II or the TNF-α systems individually leads to partial blunting of fibrosis. Incapacitating both systems, by using a combination of genetic and pharmacological means, further inhibited interstitial fibrosis and tubule atrophy in obstructive nephropathy.

scholarly journals Preferential Activity of Wild-type and Mutant Tumor Necrosis Factor-α against Tumor-derived Endothelial-like Cells

2000 ◽  
Vol 91 (1) ◽  
pp. 59-67 ◽  
Author(s):  
Kensei Kuroda ◽  
Keizo Miyata ◽  
Yasuo Tsutsumi ◽  
Shinichi Tsunoda ◽  
Koji Nishimura ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Wild Type ◽  
Factor Α ◽  
Necrosis Factor
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