<i>TNF‐α</i> and <i>IL‐10</i> polymorphisms increase the risk to hepatocellular carcinoma in HCV infected individuals

Aroucha, D.C.B.L.; Carmo, Rodrigo Feliciano do; Vasconcelos, Luydson Richardson Silva; Lima, Raul Emídio de; Mendonça, Taciana Furtado de; Arnez, Lucia Elena Alvarado; Cavalcanti, María Auxiliadora de Queiroz; Muniz, Maria Tereza Cartaxo; Aroucha, Marcílio L; Siqueira, Érika Rabelo Forte de; Pereira, Luciano Beltrão; Moura, Patrícia; Pereira, Leila Maria Moreira Beltrão; Coêlho, Maria Rosângela Cunha Duarte

doi:10.1002/jmv.24501

Cited by 27 publications

(35 citation statements)

References 63 publications

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“…In our study, the level of IL‐10 in HCV‐Cirr patients was lower compared to the CHC and HCV‐HCC patients, the cause may that IL‐10 is a stimulating factor that can regulate HSC, which is the main cellular source of extracellular matrix (ECM), from the active state back to the static state . IDO and IL‐10 are all inhibitor molecules of immune response and have been confirmed to increase in CHC patients; this characteristic may illuminate the results that IL‐10 was positively correlated with IDO among CHC patients.…”

Section: Discussionsupporting

confidence: 63%

The role of IDO, IL‐10, and TGF‐β in the HCV‐associated chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma

Yang

Gao

Chang

et al. 2018

Journal of Medical Virology

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Indoleamine-2,3-dioxygenase (IDO) is an enzyme that catalyzes tryptophan to kynurenine and studies have revealed that IDO play a vital role in regulation of liver immunity and inflammation activities. This study investigated the association between plasma IDO and disease severity and the possible marker role of IDO in the inflammatory process of hepatitis C. In this study, 80 individuals with HCV infection were retrospectively selected. Plasma levels of IDO, IL-10, and TGF-β were assayed by ELISA. Clinical characteristics of patients, including the levels of ALT, AST, and total bilirubin (TBil) were collected from clinical databases. HCV-related liver cirrhosis (HC-Cirr) and HCV-related Hepatocellular carcinoma (HCV-HCC) had significantly high plasma levels of IDO compared to other patient groups and healthy controls. Plasma IL-10 level were significantly greater in all chronic liver disease groups and with respect to TGF-β, the level was high in all the selected patients with HCV infection compare with controls. Moreover, HCV-HCC patients showed highest values for both IL-10 and TGF-β, with significant difference compared with other groups. In addition, plasma IDO was positively correlated with TGF-β among all patients with HCV infection (r = 0.4509, P < 0.0001), with IL-10 in CHC patients (r = 0.4787, P = 0.0047), with TBil in HCV-Cirr patients (r = 0.4671; P = 0.0093). High level of IDO and TGF-β is associated with hepatocyte necrosis and intrahepatic inflammation, and may be used as an index of disease progression for patients with chronic HCV infection.

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Section: Discussionsupporting

confidence: 63%

The role of IDO, IL‐10, and TGF‐β in the HCV‐associated chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma

Yang

Gao

Chang

et al. 2018

Journal of Medical Virology

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“…This is consistent with previous studies, but contradicts that reported in other works. 31,32 These inconsistent results may be partly due to small sample sizes, racial and ethnic differences, and publication bias.…”

Section: Discussionmentioning

confidence: 99%

Association of CTLA‐4, TNF alpha and IL 10 polymorphisms with susceptibility to hepatocellular carcinoma

Wang

Tai-chang

2019

Scand J Immunol

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Our aim was to evaluate the association of genetic polymorphisms of immunoregulatory molecules with susceptibility to hepatocellular carcinoma (HCC). The polymorphisms in CTLA‐4 (−318 T/C, CT60 G/A), TNF (−238 G/A, −308 G/A) and IL10 (−592 C/A, −819 C/T) were genotyped by PCR and DNA sequencing. The functional relevance of the polymorphisms was examined by ELISAs, in vitro lymphocyte proliferation assay and cytotoxic assay. The CTLA‐4 −318 TC/TT, CTLA‐4 CT60 GG, IL10 −592 CA and −819 CT/TT variants, CTLA‐4 −318 T and IL 10 −819 T alleles were positively associated with HCC risk (P < .05). While TNF −238 AA variant, TNF −238 A allele were associated with decreased risk of HCC (P < .05). Furthermore, combinations of CTLA‐4 −318 TC/TT and TNF −238 GG/GA; CTLA‐4 −318 TC/TT and IL 10 −819 CC; CTLA‐4 −318 CC and IL 10 −819 CT/TT in patients with HCC were statistically significant (P < .05). Peripheral blood mononuclear cells (PBMCs) carrying −318 TC/TT genotypes exhibited significantly lower proliferation rates, decreased IL‐2, IL‐4 levels, fewer cytolytic activities and elevated TGF‐β levels. For IL 10 −819 C/T, the CC genotype was significantly associated with higher proliferation rate, decreased TGF‐β, IL‐10 levels and higher cytolytic activities (P < .05). For TNF −238 G/A, the AA genotype only had association with serum IL‐2, IL‐4 (P < .05). In addition, we also found that CTLA‐4 −318 T/C, IL‐10 −819 T/C variants, combinations of CTLA‐4 −318 CC with IL 10 −819 CT or TT, CTLA‐4 −318 TC or TT with IL 10 −819 CT or TT were associated with the severity of HCC. These findings suggest that CTLA‐4 −318 TC/TT and IL 10 −819 CT/TT could promote the pathogenesis of HCC, which might be related with down‐regulation of Th1/Th2‐type cytokines and/or up‐regulation of Th3‐type cytokines.

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“…In a recent study in Brazil, among patients with Hepatitis C (HCV) infection with mild fibrosis, a -308 A/A SNP was found in 1.9% of the cases, and a G/A SNP in 26.1%. In patients with severe fibrosis, -308 A/A SNP in 0.8% while G/A SNP was present 21% patients 22 . Genotype AA is a rare genotype compared to genotype GG and GA 23 .…”

Section: Discussionmentioning

confidence: 97%

Detection of Tumor Necrosis Factor- (Tnf- ) Gene Promoters Polymorphism Among Liver Cirrhosis Patients With Chronic Hepatitis B Virus (Hbv) Infection in Surabaya, Indonesia

Wungu

Amin

Ruslan

et al. 2019

IJTID

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Polymorphisms in TNF-α gene promoter region are known of its role in the production of TNF-α which may influences the pathogenesis of liver disease. SNPs in positions 238 and 308 of TNF-α gene promoters may affect the production of these cytokines. This study was aimed to detect Single Nucleotide Polymorphism (SNP) on -238 and -308 positions in the TNF-α gene promoter among liver cirrhosis patients with HBV infection in Surabaya, Indonesia. This was descriptive exploratory research with cross sectional study design using serum liver cirrhosis patients with HBV infection in Endoscopy Outpatient Clinic Dr. Soetomo General Hospital, Surabaya from April-May 2017. SNPs at -238 and -308 on TNF-α gene promoter (rs361525 and rs1800629 respectively) were detected using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) with primers specific for the TNF-α promoter region and restriction enzymes NcoI and MspI. The genotypes of TNF-α gene promoter were assessed according to the length of the fragments produced in RFLP. Serum TNF-α levels was measured by commercial ELISA. In this study, as much as 149 positive HBsAg patients was found in Endoscopy Outpatient Clinic, Dr. Soetomo General Hospital, Surabaya. From those amount, as much as 30 liver cirrhosis patients with positive HBsAg were obtained. From 2/30 (6.7%) patients showed the GA heterozygote SNP either position -238 or -308. No patient had the AA genotype. Median blood TNF-α level in women (38 ng / L) was higher than in men (33 ng / L). TNF-α levels in patients with GA heterozygote genotype at -238 and -308 in this research was not different than wild-type (GG genotype). Among patients with liver cirrhosis due to chronic HBV infection in Surabaya, Indonesia, Surabaya, we found GA polymorphisms the TNF-α promoter gene at positions -238 and -308 in 6.7% patients, and did not find homozygous AA polymorphisms. Further studies including larger numbers of patients from various ethnic backgrounds in Indonesia are needed to provide robust data on TNF-α gene promoter polymorphisms and their role in the pathogenesis of liver cirrhosis with HBV infection in this country. ABSTRAKPolimorfisme pada promotor gen TNF-α diketahui berperan pada produksi TNF-α yang selanjutnya berperan dalam patogenesis penyakit hepar, penyakit infeksi, serta inflamasi. SNP gen TNF, terutama pada posisi 238 dan 308 dari promotor gen TNF-α telah diidentifikasi dapat memengaruhi produksi sitokin tersebut. Penelitian ini merupakan penelitian pendahuluan yang dilakukan untuk mendeteksi Single Nucleotide Polymorphism (SNP) promotor gen TNF-α posisi -238 dan -308 dari sampel penderita sirosis hati dengan infeksi VHB di Poli Endoskopi RSUD Dr. Soetomo, Surabaya. Jenis penelitian ini adalah penelitian deskriptif eksploratif laboratorik dengan rancangan penelitian cross sectional study yang mengambil sampel pasien penderita sirosis hati dengan infeksi VHB di Poli Endoskopi RSUD Dr. Soetomo Surabaya dari bulan April-Mei 2017. SNP posisi -238 dan -308 (rs361525 dan rs1800629) promotor gen...

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TNF‐α and IL‐10 polymorphisms increase the risk to hepatocellular carcinoma in HCV infected individuals

Cited by 27 publications

References 63 publications

The role of IDO, IL‐10, and TGF‐β in the HCV‐associated chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma

The role of IDO, IL‐10, and TGF‐β in the HCV‐associated chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma

Association of CTLA‐4, TNF alpha and IL 10 polymorphisms with susceptibility to hepatocellular carcinoma

Detection of Tumor Necrosis Factor- (Tnf- ) Gene Promoters Polymorphism Among Liver Cirrhosis Patients With Chronic Hepatitis B Virus (Hbv) Infection in Surabaya, Indonesia

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