Influence of a<i>TNF-α</i>Polymorphism on the Severity of Schistosomiasis Periportal Fibrosis in the Northeast of Brazil

Silva, Paula Carolina Valença; Gomes, Ana Cláudia Amorim; Britto, Lidiane Régia Pereira Braga de; Lima, Elker Lene Santos de; Silva, Jamile Luciana da; Montenegro, Sílvia Maria Lucena; Muniz, Maria Tereza Cartaxo; Domingues, Ana Lúcia Coutinho

doi:10.1089/gtmb.2017.0133

Cited by 8 publications

(8 citation statements)

References 26 publications

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“…Polymorphisms in the connective tissue growth factor (CTGF) as well as the IL-22 pathway were also observed. In addition, several associations have been reported between severe hepatic fibrosis during Schistosomiasis and genes encoding for IL-13, TNF-α, MAPKAP1, ST2, IL-10, M1CA, HLADRB1, IL-4, ECP, and IFN-γ, have been reported from various studies (Hirayama et al, 1998;Chevillard et al, 2003;Eriksson et al, 2007;Gong et al, 2012;Silva et al, 2014;Zhu et al, 2014;Long et al, 2015;Oliveira et al, 2015;Long et al, 2017;Silva et al, 2017). These observations suggest that while infectious agents such as schistosoma can drive hepatic fibrosis by mediating tissue damage, genetic predispositions to TGF-β pathway activation or a specific inflammatory response may make the hepatic environment conducive to fibrosis in the presence of an infectious agent.…”

Section: Parasitic Infectionsmentioning

confidence: 98%

Cellular Mechanisms of Liver Fibrosis

et al. 2021

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The liver is a central organ in the human body, coordinating several key metabolic roles. The structure of the liver which consists of the distinctive arrangement of hepatocytes, hepatic sinusoids, the hepatic artery, portal vein and the central vein, is critical for its function. Due to its unique position in the human body, the liver interacts with components of circulation targeted for the rest of the body and in the process, it is exposed to a vast array of external agents such as dietary metabolites and compounds absorbed through the intestine, including alcohol and drugs, as well as pathogens. Some of these agents may result in injury to the cellular components of liver leading to the activation of the natural wound healing response of the body or fibrogenesis. Long-term injury to liver cells and consistent activation of the fibrogenic response can lead to liver fibrosis such as that seen in chronic alcoholics or clinically obese individuals. Unidentified fibrosis can evolve into more severe consequences over a period of time such as cirrhosis and hepatocellular carcinoma. It is well recognized now that in addition to external agents, genetic predisposition also plays a role in the development of liver fibrosis. An improved understanding of the cellular pathways of fibrosis can illuminate our understanding of this process, and uncover potential therapeutic targets. Here we summarized recent aspects in the understanding of relevant pathways, cellular and molecular drivers of hepatic fibrosis and discuss how this knowledge impact the therapy of respective disease.

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Section: Parasitic Infectionsmentioning

confidence: 98%

Cellular Mechanisms of Liver Fibrosis

et al. 2021

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“…That said, studies in murine models have shown TNF to be an important mediator of granuloma formation and hepatic fibrosis ( 252 ), however, clear distinction between granuloma formation and PPF has to be drawn as we do not know how the two relate. Host genetic studies are contradictory regarding SNPs within the TNF loci; with no observable association between HLA-TNF polymorphisms and presentation with PPF in two Sudanese populations ( 253 ), but an association between a TNF gene SNP and PPF being reported for a Brazilian population ( 254 ). High TNF-alpha levels in response to SEA stimulation have also been shown to be associated with ultrasound detectable bladder morbidity due to S. haematobium infection in Kenyan case-control ( 255 ) and cross-sectional studies ( 256 ).…”

Section: The Role Of the Host In Morbidity Hotspotsmentioning

confidence: 99%

Schistosomiasis Morbidity Hotspots: Roles of the Human Host, the Parasite and Their Interface in the Development of Severe Morbidity

et al. 2021

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Schistosomiasis is the second most important human parasitic disease in terms of socioeconomic impact, causing great morbidity and mortality, predominantly across the African continent. For intestinal schistosomiasis, severe morbidity manifests as periportal fibrosis (PPF) in which large tracts of macro-fibrosis of the liver, visible by ultrasound, can occlude the main portal vein leading to portal hypertension (PHT), sequelae such as ascites and collateral vasculature, and ultimately fatalities. For urogenital schistosomiasis, severe morbidity manifests as pathology throughout the urinary system and genitals, and is a definitive cause of squamous cell bladder carcinoma. Preventative chemotherapy (PC) programmes, delivered through mass drug administration (MDA) of praziquantel (PZQ), have been at the forefront of schistosomiasis control programmes in sub-Saharan Africa since their commencement in Uganda in 2003. However, despite many successes, ‘biological hotspots’ (as distinct from ‘operational hotspots’) of both persistent high transmission and morbidity remain. In some areas, this failure to gain control of schistosomiasis has devastating consequences, with not only persistently high infection intensities, but both “subtle” and severe morbidity remaining prevalent. These hotspots highlight the requirement to revisit research into severe morbidity and its mechanisms, a topic that has been out of favor during times of PC implementation. Indeed, the focality and spatially-structured epidemiology of schistosomiasis, its transmission persistence and the morbidity induced, has long suggested that gene-environmental-interactions playing out at the host-parasite interface are crucial. Here we review evidence of potential unique parasite factors, host factors, and their gene-environmental interactions in terms of explaining differential morbidity profiles in the human host. We then take the situation of schistosomiasis mansoni within the Albertine region of Uganda as a case study in terms of elucidating the factors behind the severe morbidity observed and the avenues and directions for future research currently underway within a new research and clinical trial programme (FibroScHot).

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“…Gene polymorphisms may influence TNF-α secretion and disease susceptibility. In addition, TNF-α has been proved to be related to various diseases, such as schistosomiasis, periportal fibrosis (16) and diabetic nephropathy (17). IL-10 is also a cytokine exerting pro-inflammatory effects, and it originates from numerous cells, with a complex mechanism of action.…”

Section: Discussionmentioning

confidence: 99%

Correlation of TNF‑α and IL‑10 gene polymorphisms with primary nephrotic syndrome

et al. 2020

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The study explored the correlations of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) gene polymorphisms with susceptibility and the condition of primary nephrotic syndrome. A total of 200 patients with primary nephrotic syndrome in Qilu hospital were collected as disease group, and 200 healthy people were selected as control group. Genomic deoxyribonucleic acids (DNAs) of nucleated cells in the peripheral blood were extracted to detect the gene polymorphisms of TNF-α (rs1799724 and rs1800629) and IL-10 (rs1800872 and rs141219090). Allele distributions at rs1799724 (P=0.003) and rs1800629 (P=0.011) of TNF-α gene and at rs1800872 (P=0.033) of IL-10 gene in disease group were different from those in control group. In the disease group, allele C frequency at rs1799724 and allele A frequency at rs1800629 of TNF-α gene and allele T frequency at rs1800872 of IL-10 gene were higher. There were differences between rs1799724 (P=0.007) and rs1800629 (P=0.002) of TNF-α gene. In addition, there was a difference in the frequency of the dominant model of TNF-α gene rs1800629 between disease group and control group (P=0.035), and the frequency of dominant model GG+GA was remarkably lower in the disease group. Additionally, TT genotype at rs1799724 of TNF-α gene was obviously related to the plasma TNF-α level (P<0.05), and the plasma TNF-α level was significantly increased in disease group. AA genotype at rs141219090 of IL-10 gene had a notable correlation with the plasma IL-10 level (P<0.05), and the plasma IL-10 level in disease group was markedly raised. Additionally, CT genotype at rs1799724 of TNF-α gene was related to the 24-h urine protein level (P=0.035), GG genotype at rs1800872 of IL-10 gene was associated with the plasma albumin level (P=0.031), and GG genotype at rs141219090 was related to the serum creatinine level (P=0.047). TNF-α and IL-10 gene polymorphisms are predominantly correlated with the susceptibility and the condition of primary nephrotic syndrome.

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Influence of aTNF-αPolymorphism on the Severity of Schistosomiasis Periportal Fibrosis in the Northeast of Brazil

Abstract: Our results suggest the (-308) AA genotype may be a risk factor for severity in advanced PPF, in this Brazilian population, and could potentially be used to predict the severity of advanced PPF in schistosomiasis.

Cited by 8 publications

References 26 publications

Cellular Mechanisms of Liver Fibrosis

Cellular Mechanisms of Liver Fibrosis

Schistosomiasis Morbidity Hotspots: Roles of the Human Host, the Parasite and Their Interface in the Development of Severe Morbidity

Correlation of TNF‑α and IL‑10 gene polymorphisms with primary nephrotic syndrome

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Influence of aTNF-αPolymorphism on the Severity of Schistosomiasis Periportal Fibrosis in the Northeast of Brazil

Abstract: Our results suggest the (-308) AA genotype may be a risk factor for severity in advanced PPF, in this Brazilian population, and could potentially be used to predict the severity of advanced PPF in schistosomiasis.

Cited by 8 publications

References 26 publications

Cellular Mechanisms of Liver Fibrosis

Cellular Mechanisms of Liver Fibrosis

Schistosomiasis Morbidity Hotspots: Roles of the Human Host, the Parasite and Their Interface in the Development of Severe Morbidity

Correlation of TNF‑&alpha; and IL‑10 gene polymorphisms with primary nephrotic syndrome

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Product

Resources

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Correlation of TNF‑α and IL‑10 gene polymorphisms with primary nephrotic syndrome