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

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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.

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Abbreviations

AIH:

Autoimmune hepatitis

TNF-α:

Tumor necrosis factor-α

AMA-M2:

Anti-mitochondrial antibody-M2

EBV:

Epstein–Barr virus

ANA:

Anti-nuclear antibodies

CMV:

Cytomegalovirus

HLA:

Human leucocyte antigen

LKM1:

Anti-liver/kidney microsomal antibodies type 1

PBC:

Primary biliary cirrhosis

PSC:

Primary sclerosing cholangitis

SLA:

Antibodies against soluble liver antigen

SMA:

Smooth-muscle antibodies

ARMS PCR:

Amplification refractory mutation system polymerase chain reaction

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Acknowledgements

We thank all patients for their contribution to the study. We are indebted to Dr J Kharat, professor at the Gastroenterology Department of Habib Thameur Hospital and Dr K El Jeri, professor at the Gastroenterology Department of Charles Nicolle Hospital, for their help and their contribution. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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This research did not receive any specific Grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Correspondence to Marwa Chaouali.

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Chaouali, M., Azaiez, M.B., Tezeghdenti, A. et al. Association of TNF-α-308 Polymorphism with Susceptibility to Autoimmune Hepatitis in Tunisians. Biochem Genet 56, 650–662 (2018). https://doi.org/10.1007/s10528-018-9867-4

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