TGF-β1 gene - 509C > T promoter polymorphism modulates TGF-β1 levels in hepatitis E patients.
Elevated levels of transforming growth factor-β1 (TGF-β1) and its positive correlation with Foxp3 expression in hepatitis E patients have indicated involvement of TGF-β1 in hepatitis E pathogenesis. The current study determined polymorphisms in TGF-β1 gene, plasma TGF-β1 levels and T effector (Teff) cell proliferation and explored their association in a case control study. Polymorphisms in three selected sites (- 509C > T, + 869T > C and + 915G > C) of TGF-β1 gene by PCR & restriction fragment length polymorphism methods, plasma TGF-β1 quantitation by ELISA and Teff (CD4 + CD25 -) cell proliferation by CFSE method were carried out in 277 hepatitis E patients (HE) with self-limiting infection and 233 ethnically matched healthy controls (HCs) from western India. Frequency of CT genotype of - 509C > T site was significantly higher in hepatitis E patients compared to healthy controls (p = 0.017; OR 1.53, 95% CI 1.07-2.17). Plasma TGF-β1 levels were significantly higher in HE compared to HCs. TGF-β1 level of patient group having CT genotype of - 509C > T site was significantly higher compared to those having CC or TT genotypes. Teff cell proliferation was negatively correlated with plasma TGF-β1 levels in HE patients (r = - 0.568; p = 0.014). Influence of TGF-β1 promoter (- 509C > T) polymorphism on plasma TGF-β1 levels and inverse correlation of Teff cell proliferation with plasma TGF-β1 levels in self-limiting hepatitis E patients suggest key role of TGF-β1 in augmentation of reported T regulatory cell mediated pathogenesis in hepatitis E.
Hepatitis Group, National Institute of Virology, Pune, India.
Sanjay B
SB
Rathod
Hepatitis Group, National Institute of Virology, Pune, India.
Anuradha S
AS
Tripathy
ALT, alanine transaminase; CI, confidence interval; HBV, hepatitis B virus; HCV, hepatitis C virus; HCs, healthy controls; HE, hepatitis E patients; HEV, hepatitis E virus; Hepatitis E; OR, odds ratio; PBMCs, peripheral blood mononuclear cells; RFLP, restriction fragment length polymorphism; Restriction fragment length polymorphism; Single nucleotide polymorphism; T effector cell proliferation; TGF-β1, transforming growth factor beta 1; Teff, T effector cells; Transforming growth factor beta 1; Treg, T regulatory cells