Association of TGF‐β1 codon 25 (G915C) polymorphism with hepatitis C virus infection

Abstract

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‐α (−308G/A [rs1800629]), TGF‐β1 (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‐γ (+874T/A [rs2430561]). This study demonstrated a statistically significant difference in the frequency of TGF‐β1 codon 25 polymorphism between healthy subjects and those infected with HCV. No associations were observed between polymorphisms of TNF‐α, IFN‐γ, IL‐10, TGF‐β1 codon 10, and IL‐6 and HCV infection. These findings suggest that TGF‐β1 codon 25 polymorphism could be a host genetic factor associated with susceptibility to HCV infection. J. Med. Virol. 80:58–64, 2008. © 2007 Wiley‐Liss, Inc.

Regulation of the Immune Response by TGF-β: From Conception to Autoimmunity and Infection

“…Furthermore, TGFB1 genetic polymorphisms have been associated with higher systemic TGF-b levels and worse outcome in hepatic viral infections (Dai et al 2008;Pereira et al 2008). Viral-specific proteins have also been shown to enhance TGF-b production and its cellular activity.…”

Association between TGFB1 915G/C polymorphism and susceptibility to chronic hepatitis C virus infection: A meta-analysis

“…1. Finally, 8 eligible studies including a total of 1,542 participants (910 cases and 632 controls) were identified (14)(15)(16)(17)(18)(19)(20)(21). A summary of the characteristics of each study, including first author, year of publication, ethnicity of cases and controls, genotyping methods, number of cases and Table I.…”

“…However, two studies were outside the expected 95% CI of Begg's funnel plot in the C vs. G, GC vs. GG and CC+GC vs. GG models. After excluding these two studies contributing to heterogeneity (16,18), there was no obvious asymmetry of Begg's funnel plot in the C vs. G, GC vs. GG and CC+GC vs. GG models, with Egger's test P=0.110, 0.147 and 0.204, respectively.…”

“…TGF-β1, the expression product of TGFB1, is a polypeptide that is mainly secreted by regulatory T cells (Tregs) (35,36) and was previouly associated with the development of chronic HCV infection (37). Tregs have been reported to suppress T-cell immune responses through the secretion of cytokines, including TGF-β1 (16). HCV infection is characterized by the impairment of HCV-specific effector T-cell responses, suggesting that TGF-β1, as an effector cytokine, possibly contributes to the long-term persistence of HCV infection (16).…”

“…The G→C transition at position 915 of the TGF-β1 signal sequence causes the amino acid sequence to change from arginine to proline in codon 25. A number of previous studies reported the association between this SNP and susceptibility to chronic HCV infection (14)(15)(16)(17)(18)(19)(20)(21). However, the currently available results are controversial.…”