Hepatitis-related hepatocellular carcinoma: Insights into cytokine gene polymorphisms

Dondeti, Mahmoud F.; El-maadawy, Eman A.; Talaat, Roba M.

doi:10.3748/wjg.v22.i30.6800

Cited by 36 publications

(33 citation statements)

References 214 publications

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“…This comes in alignment with previous reports, which showed the disturbed healing process in NASH contributed to fibrosis progression via chronic activation of type 2 inflammation manifested by increased serum IL-13 levels [9,10]. It was explained by overproduction of Th2 cytokines, which typically promote B-cell hyperactivity and humoral immune responses, whereas T cell hyperactivity and inflammation frequently associated with an excess of Th1 and Th17 cytokines at earlier stages of the diseases [55]. However, IL-4/IL-13-secreting invariant nature killer T cells (iNKT) were prevalent later in the disease [56].…”

Section: Discussionsupporting

confidence: 90%

Polymorphisms in Interleukin 13 Signaling and Interacting Genes Predict Advanced Fibrosis and Hepatocellular Carcinoma Development in Non-Alcoholic Steatohepatitis

El-Derany

2020

Biology

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Background: non-alcoholic steatohepatitis (NASH) recently headlined hepatocellular carcinoma (HCC) worldwide. This study aims to unveil the role of some unaddressed critical players that might aid in understanding, predicting, and targeting NASH and NASH-HCC. Methods: Serum interleukin 13 (IL-13) levels and single nucleotide polymorphisms (SNPs) within interleukin (IL)-13 rs20541, IL-13 receptors (IL-13R1) rs2248841, (IL-13R2) rs5946040, signal transducer activator of transcription 6 (STAT6) rs167769, yes-associated protein (YAP1) rs11225163, programmed death-ligand 1 (PD-L1) rs2282055, and programmed death-ligand 2 (PD-L2) rs7854413 genes were analyzed by qRT-PCR. Multiple stepwise regression analysis was performed on a cohort of 134 Egyptian male patients diagnosed with NASH and NASH-HCC. RESULTS: higher serum alpha-fetoprotein (AFP) and higher serum IL-13 levels were directly associated with HCC development in NASH (odds ratio (OR) 19.6 and 1.9 p < 0.01). Reversibly, the presence of the C/C genotype in STAT6 rs167769 and the C allele carrier YAP1 rs11225163 were inversely associated with HCC in NASH patients (OR 0.015 and 0.047 p < 0.01). A predictive model was formulated with 97.5% specificity, 90.9% sensitivity, and 94.8% accuracy. Moreover, higher serum IL-13 levels and the presence of PD-L2 rs7854413 C allele carriers were associated with advanced fibrosis progression in NASH patients (OR 1.432 and 3.797 p < 0.01). Serum levels of IL-13 and C/C genotype in STAT6 rs167769 significantly increased the predictive capacity of serum AFP to predict HCC in F1–F2 and in F3–F4 fibrosis grades NASH patients. Conclusion: association between serum IL-13 and PD-L2 rs7854413 polymorphism successfully predict advanced fibrosis in NASH. However, HCC development in NASH is associated with higher serum AFP, IL-13 levels, and STAT6 rs167769, YAP1 rs11225163 polymorphisms.

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Section: Discussionsupporting

confidence: 90%

Polymorphisms in Interleukin 13 Signaling and Interacting Genes Predict Advanced Fibrosis and Hepatocellular Carcinoma Development in Non-Alcoholic Steatohepatitis

El-Derany

2020

Biology

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“…Hepatitis virus infections are now recognized as the main causative agent of hepatocellular carcinoma. Nevertheless, genetic predisposition may influence the viral persistence and increase the risk of hepatocellular carcinoma . IL‐1RN allele 2 may play a protective role in the development of hepatitis B infection, and the IL‐1β CC genotype may be associated with HBV‐DNA replication .…”

Section: Il‐1 and Malignanciesmentioning

confidence: 99%

“…Nevertheless, genetic predisposition may influence the viral persistence and increase the risk of hepatocellular carcinoma. 171 IL-1RN allele 2 may play a protective role in the development of hepatitis B infection, and the IL-1β CC genotype may be associated with HBV-DNA replication. 172 The IL-1β-511C allele is associated with the high IL-1β production in the liver and was identified as a marker for the development of hepatocellular carcinoma patients with chronic hepatitis B infection.…”

Section: Il-1 and Malignanciesmentioning

confidence: 99%

Interleukin 1 gene polymorphism and susceptibility to disease

Khazim

Azulay

Kristal

et al. 2017

Immunological Reviews

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The Interleukin 1 (IL-1) family plays a central role in the generation and regulation of inflammatory responses, in both innate and adaptive immunity. Although the IL-1 molecules are traditionally considered to be classical proinflammatory cytokines, their functions are not restricted to inflammation, and they have also been shown to play a key role in a wide range of additional physiological and pathological functions, including learning modulation, sleep, pregnancy, depression, appetite, hematopoiesis, metabolism, and many others. Since their effect as cytokines and regulators of inflammation is so pleiotropic, any shift of the biological balance between agonistic and antagonistic signals has the potential to cause disease. Here, we consider the genetic influence of interleukin-1 gene polymorphism in the context of susceptibility to human diseases. We review known single nucleotide polymorphisms (SNP) of IL-1 genes linked to human diseases, and suggest how exploring biological effects of IL-1 gene cluster polymorphism may lead to new directions in understanding and diagnostic of disease and effective treatment.

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“…In our study, 12 eligible studies involved IL-10-1082A/G and IL-10-592C/A polymorphisms (Dondeti, El-maadawy, & Talaat, 2016, Gao et al, 2016,Gusatti et al, 2016, Yao et al, 2015, Manjita et al, 2014, Sofian et al, 2013Ge et al, 2009, Baghi, Alavian, Mehrnoush, & Salimi, 2015, Q. Gao et al, 2017) Sofian et al, 2013, 8 eligible studies involved INF-γ +874 (Heidari et al, 2016, Yao et al, 2015, Migita et al, 2005, Ognjanovic, Yuan, Chaptman, Fan, & Yu, 2009, 9 studies involved TNF-α (Panigrahi et al, 2014, Gusatti et al, 2016, Panigrahi et al, 2014, Migita et al, 2005, Q. Gao et al, 2017, Ognjanovic et al, 2009, Kim et al, 2018, Fletcher et al, 2011 and 5 studies involved VDR (Falleti et al, 2010,Suneetha et al, 2006, Peng et al, 2014, Elmer, Tuncbilek, Aydin, & Hizel, 2013, X. Yao et al, 2013. The numbers of quality scores for each study for each study were summarized in Table 1.…”

Section: Resultsmentioning

confidence: 99%

“…Interleukin 10 (IL-10) gene has three single nucleotide polymorphisms in the promoter region located at -1082A/G, -819T/C and -592A/C upstream of the transcription initiation site(F. Wang, 2003, Dondeti, El-maadawy, & Talaat, 2016. Polymorphisms in the IL-10 promoter gene will affect its expression and being a potent inhibitor of Th1 cytokines, the expression of Th1 cytokines will be affected.…”

Section: Introductionmentioning

confidence: 99%

Host genetic factors associated with hepatitis B virus infection and progression to chronic disease: A systematic review and Meta analysis

Kafeero¹,

Ndagire²,

Nanyingi³

et al. 2019

Preprint

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Back ground Contradicting results from many laboratories on the role of genetic factors in the susceptibility/resistance to hepatitis B infection have been reported. In this review we examined 27 published full research articles and assessed the role of Th1/Th2 cytokine promoter and vitamin D receptor gene polymorphisms. We summarized the available data on the relationship between the gene polymorphisms and susceptibility/resistance to hepatitis B virus infection together with likely disease evolution to come up with candidate single nucleotide polymorphisms implicated in the disease state with the population. Method The study was done in tandem with the PRISMA standards and the Cochran’s Q test, I2 statistics for heterogeneity and the Odds ratio were calculated using a commercially available soft ware called MedCalcs (http://www.medcalc.org). A random effects model was used to pool the odds ratio for heterogeneities ≥50% or else a fixed effects model was used. All analyses were done at 95% Confidence Interval and a P<0.05 was considered statistically significant. Results We found that IL-10-592C/A genotype AA (P=0.017, OR=0.752, 95%CI=0.595 to 0.950) and TNF-α-238G/A genotype AA+ AG (P<0.001, OR=0.407, 95%CI=0.005 to 30.1) were significantly associated with reduced risk of hepatitis B infection by the random effects model. TNF-α-238G/A genotype GG had the risk of chronic infection (OR=3.587, 95% CI= 0.127 to 101.176) under the random effect model. Most of the other SNPs had borderline risk of HBV infection (OR 0.6 to 1.12) with a few cases of high risk, IL-10-1082A/G genotype AA (OR=1.608, 95%CI=0.861 to 3.003) and reduced risk, IL-10-1082A/G genotype AG (OR=0.485, 95% CI=0.232 to 1.014) Conclusion We found that IL-10-592C/A genotype AA and TNF-α-238G/A genotype AA+ AG were significantly associated with reduced risk of hepatitis B infection.

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Hepatitis-related hepatocellular carcinoma: Insights into cytokine gene polymorphisms

Cited by 36 publications

References 214 publications

Polymorphisms in Interleukin 13 Signaling and Interacting Genes Predict Advanced Fibrosis and Hepatocellular Carcinoma Development in Non-Alcoholic Steatohepatitis

Polymorphisms in Interleukin 13 Signaling and Interacting Genes Predict Advanced Fibrosis and Hepatocellular Carcinoma Development in Non-Alcoholic Steatohepatitis

Interleukin 1 gene polymorphism and susceptibility to disease

Host genetic factors associated with hepatitis B virus infection and progression to chronic disease: A systematic review and Meta analysis

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