Association between the epidermal growth factor rs4444903 G/G genotype and advanced fibrosis at a young age in chronic hepatitis C

Falleti, Edmondo; Cmet, Sara; Fabris, Carlo; Bitetto, Davide; Cussigh, Annarosa; Fornasiere, Ezio; Bignulin, E.; Feruglio, Cristina; Mosanghini, Elena; Fontanini, Elisabetta; Pirisi, Mario; Toniutto, Pierluigi

doi:10.1016/j.cyto.2011.10.018

Cited by 12 publications

(14 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It might be that EGF expression alone is not powerful enough to predict prognosis, or it could be that EGF expression in the surrounding, nontumoral tissue will have greater prognostic value. Consistent with this, Falleti et al35 reported that the EGF genotype associates with advanced fibrosis at a young age in HCV patients. They hypothesized that the EGF polymorphism is responsible for a more rapid disease progression early in the course of HCV infection, which would be consistent with its role in cellular entry.…”

Section: Discussionmentioning

confidence: 55%

A functional polymorphism in the epidermal growth factor gene predicts hepatocellular carcinoma risk in Japanese hepatitis C patients

Suenaga¹,

Yamada²,

Fujii³

et al. 2013

OTT

View full text Add to dashboard Cite

BackgroundA single nucleotide polymorphism (SNP) in the epidermal growth factor (EGF) gene (rs4444903) has been associated with increased risk of cancer, including hepatocellular carcinoma (HCC). The aim of this study was to examine the relationship between the EGF SNP genotype and the development and prognosis of HCC, in a Japanese population.MethodsRestriction fragment-length polymorphism was used to determine the presence of the EGF SNP genotype in 498 patients, including 208 patients with HCC. The level of EGF messenger ribonucleic acid (mRNA) expression in cancerous tissues was measured by quantitative reverse transcription polymerase chain reaction. The correlation between the EGF SNP genotype and prognosis was statistically analyzed in the patients with HCC.ResultsThe proportion of the A/A, A/G, and G/G genotypes were 5.3%, 42.8%, and 51.9%, respectively, in the patients with HCC, whereas in those without HCC, they were 8.6%, 35.9%, and 55.5%, respectively, revealing that the odds ratio (OR) of developing HCC was higher in patients with a G allele (OR =1.94, P=0.080 for A/G patients and OR =1.52, P=0.261 for G/G patients, as compared with A/A patients). In particular, when the analysis was limited to the 363 patients with hepatitis C, the OR for developing HCC was 3.54 (P=0.014) for A/G patients and was 2.85 (P=0.042) for G/G patients, as compared with A/A patients. Tumoral EGF mRNA expression in G/G patients was significantly higher than that in A/A patients (P=0.033). No statistically significant differences were observed between the EGF SNP genotype and diseasefree or overall survival.ConclusionThe EGF SNP genotype might be associated with a risk for the development of HCC in Japanese patients but not with prognosis. Of note, the association is significantly stronger in patients with hepatitis C, which is the main risk factor for HCC in Japan.

show abstract

Section: Discussionmentioning

confidence: 55%

A functional polymorphism in the epidermal growth factor gene predicts hepatocellular carcinoma risk in Japanese hepatitis C patients

Suenaga¹,

Yamada²,

Fujii³

et al. 2013

OTT

View full text Add to dashboard Cite

show abstract

“…Our finding of an increased risk of development of graft cirrhosis in patients with the EGF non-AA compared to AA genotype is consistent with prior data regarding the EGF locus and clinical outcome in the non-transplant setting. In a cross-sectional study, the G allele of EGF rs4444903 was associated with higher degrees of liver fibrosis in younger subjects with CHC (7). Additionally, we previously found an association between EGF non-AA genotype and increased risk of clinical deterioration among HCV cirrhotics (8).…”

Section: Discussionmentioning

confidence: 99%

“…The EGF A>G polymorphism rs4444903 has been associated with increased EGF levels (5), increased risk of hepatocellular carcinoma (HCC) (5, 6), increased fibrosis (7), and hepatic decompensation (8). The PNPLA3 C>G polymorphism rs738409 is associated with steatosis, fibrosis (9, 10), and HCC (10, 11).…”

mentioning

confidence: 99%

Impact of EGF,IL28B, and PNPLA3 polymorphisms on the outcome of allograft hepatitis C: a multicenter study

Mueller

King

Johnson

et al. 2016

Clinical Transplantation

View full text Add to dashboard Cite

Hepatitis C virus (HCV) infection is accelerated following liver transplantation (LT). Single nucleotide polymorphisms (SNPs) near the epidermal growth factor (EGF) (rs4444903), IL28B (rs12979860), and PNPLA3 (rs738409) loci are associated with treatment response, fibrosis, and hepatocellular carcinoma in non-transplant hepatitis C, but allograft population data are limited. We sought to determine the role of these SNPs in 264 patients with HCV who underwent LT between 1990 and 2008. Genotypes were determined from donor wedge/allograft biopsies and recipient explants. Cox proportional hazards model was used to assess time to cirrhosis, liver-related death, and retransplantation, adjusting for donor age and sustained virological response (SVR). Over a median follow-up of 6.3 yr, a trend toward increased progression to graft cirrhosis was observed among recipients of an EGF non-AA vs. AA donor liver (adjusted HR 2.01; 95% CI 0.93–4.34; p = 0.08). No other genotypes predicted cirrhosis development or graft survival. The CC IL28B variant in both recipients and donors was associated with increased rate of SVR (R-CC/D-CC 8/12[67%], R-non-CC/D-CC or R-CC/D-non-CC 23/52[44%], R-non-CC/D-non-CC 12/45[27%], p linear trend = 0.009). Recipient EGF, IL28B, and PNPLA3, and donor IL28B and PNPLA3 genotypes do not predict adverse outcomes in HCV LT recipients. A potential association exists between donor EGF genotype and cirrhosis.

show abstract

“…Many other studies with only small numbers of HCV patients showed association between fibrosis progression and genetic polymorphisms of different genes such as interferon-y receptor, tumour necrosis factor alpha promoter, chemokine receptor 5, RANTES, MCP-2, Interleukin-10, complement factor 5, chemokine scavenger receptor D6, mannan-binding lectin 2, low-density lipoprotein receptor, Factor V Leiden, Factor VII-activating protease antizyme inhibitor (AzI), human platelets antigen (HPA), apolipoprotein E and epidermal growth factor (EGF) [100,101,102,103,104,105,106,107,108,109,110,111,112,113,114]. The list of different genes is not complete and there is a lack of further replication and validation studies with larger numbers of patients.…”

Section: Host Genetics and Chronic Complications Such As Fibrosis mentioning

confidence: 99%

Host Genetic Variants in the Pathogenesis of Hepatitis C

Rau

Baur

Geier

2012

Viruses

View full text Add to dashboard Cite

Direct-acting antiviral drugs (DAAs) are currently replacing antiviral therapy for Hepatitis C infection. Treatment related side effects are even worse and the emergence of resistant viruses must be avoided because of the direct-antiviral action. Altogether it remains a challenge to take treatment decisions in a clinical setting with cost restrictions. Genetic host factors are hereby essential to implement an individualized treatment concept. In recent years results on different genetic variants have been published with a strong association with therapy response, fibrosis and treatment-related side effects. Polymorphisms of the IL28B gene were identified as accurate predictors for therapy response and spontaneous clearance of HCV infection and are already used for diagnostic decisions. For RBV-induced side effects, such as hemolytic anemia, associations to genetic variants of inosine triphosphatase (ITPA) were described and different SLC28 transporters for RBV-uptake have been successfully analyzed. Fibrosis progression has been associated with variants of Vitamin D receptor (VDR) and ABCB11 (bile salt export pump). Cirrhotic patients especially have a high treatment risk and low therapy response, so that personalized antiviral treatment is mandatory. This review focuses on different host genetic variants in the pathogenesis of Hepatitis C at the beginning of a new area of treatment.

show abstract

Association between the epidermal growth factor rs4444903 G/G genotype and advanced fibrosis at a young age in chronic hepatitis C

Cited by 12 publications

References 32 publications

A functional polymorphism in the epidermal growth factor gene predicts hepatocellular carcinoma risk in Japanese hepatitis C patients

A functional polymorphism in the epidermal growth factor gene predicts hepatocellular carcinoma risk in Japanese hepatitis C patients

Impact of EGF,IL28B, and PNPLA3 polymorphisms on the outcome of allograft hepatitis C: a multicenter study

Host Genetic Variants in the Pathogenesis of Hepatitis C

Contact Info

Product

Resources

About