Polymorphisms in tumour necrosis factor-alpha, transforming growth factor-beta, interleukin-10, interleukin-6, interferon-gamma, and outcome of hepatitis C virus infection.

Cytokines play a key role in the regulation of immune responses. In hepatitis C virus infection (HCV), the production of inappropriate cytokine levels appears to contribute to viral persistence and to affect response to therapy. Cytokine genes are polymorphic at specific sites, and certain mutations located within coding/regulatory regions have been shown to affect the overall expression and secretion of cytokines. The aim of this study was to investigate the frequency of genotypes associated with polymorphisms of TNF-alpha, TGF-beta, IL-10, IL-6, and IFN-gamma and to determine their association with the outcome of HCV infection. Genotyping was carried out by polymerase chain reaction sequence-specific primers on genomic DNA isolated from 158 individuals. Of these, 66 had spontaneously recovered from infection (persistently HCV RNA negative), while 92 had persistent infection (persistently HCV RNA positive). All patients were genotyped as high or low producers of TNF-alpha and IL-6 and high, intermediate, or low producers of TGF-beta, IL-10, and IFN-gamma based on single nucleotide substitutions. A significant proportion of patients with viral clearance were genotyped with a low IL-6 production profile, whereas those with persistent infection were genotyped with a high production profile (P = 0.02). No associations were observed between polymorphisms of TNF-alpha, IL-10, or IFN-gamma and viral clearance or persistent infection. Furthermore, there were no associations between cytokine genotypes and severity of disease. Inheritance of some genotypes associated with polymorphisms of cytokine genes, such as IL-6, may be host genetic factors associated with outcome of HCV in a well-defined ethnically homogeneous cohort.

Barrett S ，Collins M ，Kenny C ，Ryan E ，Keane CO ，Crowe J ... -  《JOURNAL OF MEDICAL VIROLOGY》

Association of TGF-beta1 codon 25 (G915C) polymorphism with hepatitis C virus infection.

Cytokines play a key role in the regulation of immune responses. In hepatitis C virus infection (HCV), the production of abnormal cytokine levels appears to contribute to the progression of the disease, viral persistence, and affects response to therapy. Cytokine genes are polymorphic at specific sites, and certain polymorphisms located within coding/regulatory regions have been shown to affect the overall expression and secretion of cytokines. The aim of the present study was to identify potential markers of cytokines genes associated with the susceptibility to HCV infection. The cohort was composed of 128 individuals infected by HCV and 94 healthy controls. Genotyping was carried out by PCR-SSP. The distributions of the following polymorphisms were compared in these groups: TNF-alpha (-308G/A [rs1800629]), TGF-beta1 (codon 10 T/C [rs1982073], codon 25 G/C [rs1800471]), IL-10 (-1082 A/G [rs 1800896]; -819T/C [rs1800871]; -592A/C [rs 1800872]), IL-6 (-174G/C [rs1800795]), and IFN-gamma (+874T/A [rs2430561]). This study demonstrated a statistically significant difference in the frequency of TGF-beta1 codon 25 polymorphism between healthy subjects and those infected with HCV. No associations were observed between polymorphisms of TNF-alpha, IFN-gamma, IL-10, TGF-beta1 codon 10, and IL-6 and HCV infection. These findings suggest that TGF-beta1 codon 25 polymorphism could be a host genetic factor associated with susceptibility to HCV infection.

Pereira FA ，Pinheiro da Silva NN ，Rodart IF ，Carmo TM ，Lemaire DC ，Reis MG ... -  《JOURNAL OF MEDICAL VIROLOGY》

Role of cytokine gene polymorphism and hepatic transforming growth factor beta1 expression in recurrent hepatitis C after liver transplantation.

Ben-Ari Z ，Pappo O ，Druzd T ，Sulkes J ，Klein T ，Samra Z ，Gadba R ，Tambur AR ，Tur-Kaspa R ，Mor E ... -  《CYTOKINE》

The involvement of IL-10, IL-6, IFN-gamma, TNF-alpha and TGF-beta gene polymorphisms among Turkish lung cancer patients.

Colakogullari M ，Ulukaya E ，Yilmaztepe Oral A ，Aymak F ，Basturk B ，Ursavas A ，Oral HB ... -  《-》

Cytokine gene polymorphisms in patients infected with hepatitis B virus.

Ben-Ari Z ，Mor E ，Papo O ，Kfir B ，Sulkes J ，Tambur AR ，Tur-Kaspa R ，Klein T ... -  《AMERICAN JOURNAL OF GASTROENTEROLOGY》