Association of TNF-α-308 Polymorphism with Susceptibility to Autoimmune Hepatitis in Tunisians

Abstract

Autoimmune hepatitis (AIH) is a chronic hepatitis of unknown etiology and several proinflammatory cytokines are implicated in its pathogenesis. The association of TNF-α gene polymorphism with AIH onset is not fully elucidated especially in the Tunisian population. The aim of this study was to determine the association of TNF-α (-308 G > A) polymorphism with AIH susceptibility and with TNF-α expression or clinical manifestations of AIH. A total of 50 AIH patients and 150 controls were included. Evaluation of TNF-α polymorphism was performed by ARMS PCR method. A significantly higher frequence of the AA genotype was found in AIH patients compared to controls (34 vs. 8%, p = 0.00002, OR 5.88). The frequency of the A-allele was significantly higher in patients with AIH compared to controls (55 vs. 37.3%, p = 0.002, OR 2.05). The G-allele was significantly more frequent in healthy controls compared to AIH patients [43 vs. 61.3%, p = 0.001, OR 0.47 (0.3-0.75)]. There was a positive correlation between the A/A genotype and a higher serum expression of TNF-α. The TNF*A allele confer susceptibility to AIH in the Tunisian patients and is associated with increased production of TNF-α. Anti-TNF antibodies could be an alternative to the use of corticotherapy and may avoid the exacerbated immune response in AIH.

Keywords: Autoimmune hepatitis; TNF-α gene polymorphisms; Tumor necrosis factor-α.