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Inflammasome Genes' Polymorphisms in Egyptian Chronic Hepatitis C Patients: Influence on Vulnerability to Infection and Response to Treatment.

ABSTRACT: Chronic inflammation is a pivotal contributor to the liver damage mediated by hepatitis C virus (HCV). The NOD-like receptor, pyrin domain-containing 3 (NLRP3) inflammasome is activated by HCV in both hepatocytes and Kupffer cells. The aim of our study was to investigate the association of nine single-nucleotide polymorphisms in four inflammasome genes (NLRP3, CARD8, IL-1?, and IL-18) with the susceptibility to HCV infection and outcome of interferon treatment in 201 Egyptian chronic hepatitis C patients and 95 healthy controls. The genotyping was conducted using TaqMan predesigned SNP assay. In the comparative analysis, the CC genotype of the NLRP3 rs1539019 was found to be associated with the lower risk to chronic HCV infection (OR: 0.33, 95% CI: 0.17-0.62). This association was also found for the CA genotype and the A allele of the NLRP3 rs35829419 (OR: 0.18 and 0.22, respectively), in addition to the GG genotype and G allele of IL-18 rs1946518 (OR: 0.55 and 0.61, respectively). In contrast, the AA genotype of the IL-1? rs1143629 was significantly more frequent in HCV patients (OR: 1.7, 95% CI: 1-2.86). Notably, the frequency of the AA genotype of NLRP3 rs1539019 was significantly higher in patients with lack of response (NR) to the interferon treatment (OR: 1.95, 95% CI: 1-3.7). A similar association was found for both the CC genotype and C allele of the NLRP3 rs35829419 (OR: 2.78 and 2.73, respectively) and for the TT genotype and T allele of CARD8 rs2043211 (OR: 2.64 and 1.54, respectively). Yet, the IL-1? (rs1143629, rs1143634) and IL-18 (rs187238, rs1946518) polymorphisms did not show any significant association with response to interferon treatment. In conclusion, this study reports, for the first time, the association of genetic variations in NLRP3 with hepatitis C susceptibility and response to treatment in Egyptian patients. However, further large-scale studies are recommended to confirm our findings.

SUBMITTER: Estfanous SZK

PROVIDER: S-EPMC6343134 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Inflammasome Genes' Polymorphisms in Egyptian Chronic Hepatitis C Patients: Influence on Vulnerability to Infection and Response to Treatment.

Estfanous Shady Z K SZK Ali Sahar A SA Seif Sameh M SM Soror Sameh H A SHA Abdelaziz Dalia H A DHA

Mediators of inflammation 20190109

Chronic inflammation is a pivotal contributor to the liver damage mediated by hepatitis C virus (HCV). The NOD-like receptor, pyrin domain-containing 3 (NLRP3) inflammasome is activated by HCV in both hepatocytes and Kupffer cells. The aim of our study was to investigate the association of nine single-nucleotide polymorphisms in four inflammasome genes (NLRP3, CARD8, IL-1<i>β</i>, and IL-18) with the susceptibility to HCV infection and outcome of interferon treatment in 201 Egyptian chronic hepa ...[more]

PMID: 30728751

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Project description:Hepatitis C is considered a major public health problem caused by the hepatitis C virus (HCV). Viral infections are known to induce production of IL1β through the signaling pathway of inflammasomes. Emerging evidences suggest that Inflammasome genes may influence the immune response against HCV as the host genetic background may contribute to the balance between acute and chronic inflammation. We investigated in 151 patients with chronic hepatitis C and 206 healthy blood donors' individuals (HD). Polymorphisms in the IL1B and IL18 genes were genotyped by PCR-RFLP, while NLRP3, CARD8, CTSB and AIM2 by RT- PCR. Serum assay of IL-1β cytokine was performed by ELISA. 84 patients presented mild fibrosis (<F2) and 67 advanced fibrosis (≥ F2). Among the HD individuals the NLRP3-rs10754558 C/C genotype correlated with higher IL-1β levels compared to the G/G genotype. Similar pattern was observed in patients with hepatitis C, mean circulating IL-1β levels were 21,96 ± 4.5 and 10,62 ± 3.3pg/mL among the C/C and G/G genotypes, respectively. This pattern holds even after stratification of the patients into mild fibrosis and advanced fibrosis, demonstrating that the NLRP3-rs10754558 or another polymorphism in linkage disequilibrium with it possibly has an influence on the processing of pro-IL-1β. Notably, higher levels of IL-1β (Mann-Whitney test, p<0.0001) were observed among patients (mean ± SEM: 19,24 ±3.pg/mL) when compared with controls (mean ± SEM: 11,80 ±1.0pg/mL). Gene-gene interaction showed that individuals heterogyzotes for both CARD8-rs2009373 and IL1B-rs16944 are less prone to hepatitis C development (padj = 0.039). Similarly, herozygote carriers for CTSB-rs1692816 and AIM2-rs1103577 (padj = 0.008) or for IL18-rs187238 and NLRP3-rs10754558 (padj = 0.005), have less chances to the development of hepatitis C. However, between subgroups of <F2 and ≥F2, individuals homozygous for the T allele of CARD8-rs2009373 and heterozygous for IL18-rs187238 (padj = 0.028), have mild form of fibrosis.

Project description:BACKGROUND: Hepatitis G virus (HGV) is an RNA virus. It is mainly transmitted through exposure to contaminated blood although other routes may also exist. Patients with chronic renal failure (CRF) are at high risk of acquiring HGV because they require frequent blood transfusions. Ongoing HGV infection can be only diagnosed by demonstrating viremia in patient sample by reverse transcriptase (RT) PCR. Antibodies to the envelop protein E2 (anti E2) of HGV is an indicator of virus clearance and testify past HGV contact. This cross sectional study was done to assess the frequency of HGV exposure (ongoing and past infection) in Egyptian children with CRF and to study the possible risk factors of infection. METHODS: This study included 100 children with CRF [34 on regular haemodialysis (HD) and 66 before the start of dialysis (predialysis)]. All patients sera were tested for HGV RNA by RT-PCR, anti E2, hepatitis C virus (HCV) antibody, hepatitis B surface antigen (HBsAg), and hepatitis B core antibody (HBcAB). Twenty five healthy children of matched age & sex were used as controls. RESULTS: HGV RNA was positive in 9 (26.5%) of HD and 9 (13.6%) of predialysis children. Anti E2 was positive in 14 (41.2%) of HD and 19 (28.8%) of predialysis children.In comparison to controls; CRF (n = 100); HD and predialysis children had significantly higher prevalence of anti E2 [4% VS 33% for all CRF cases; (p = 0.002)& 41.2% (p = 0.002) and 28.8% (p = 0.01); for HD and predialysis groups; respectively]. HGV RNA was significantly more prevalent only in HD children in comparison to controls (p = 0.03). HD and predialysis children did not have significant difference in the prevalence of HGV RNA (p = 0.16) or anti E2 (p = 0.26).HGV exposure was not correlated with positivity of anti HCV (p = 0.32), HCV RNA (0.09), HBsAg/HBcAB (p = 1), age (p = 0.06), or gender (p = 0.83). It was significantly correlated with duration of the disease (p < 0.001). Ongoing HGV infection was significantly more prevalent with frequent blood transfusion (p < 0.001). There were no significant differences in serum levels of ALT (p = 0.09), total bilirubin (p = 0.1) and albumin (p = 0.06) in children with ongoing infection in comparison to healthy controls. CONCLUSIONS: The frequency of HGV exposure in Egyptian children with CRF appears to be high and is mainly related to frequent blood transfusions and longer disease duration. HGV infection in these children is not associated with significant changes in hepatic biochemical parameters.

Dataset Information

Inflammasome Genes' Polymorphisms in Egyptian Chronic Hepatitis C Patients: Influence on Vulnerability to Infection and Response to Treatment.

Publications

Inflammasome Genes' Polymorphisms in Egyptian Chronic Hepatitis C Patients: Influence on Vulnerability to Infection and Response to Treatment.

Similar Datasets

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