Tumour necrosis factor alpha (TNF-α) genetic polymorphisms and the risk of autoimmune liver disease: a meta-analysis

Epidemiological studies have evaluated the association between tumour necrosis factor alpha (TNF-α)- 308G/A and (TNF-α)- 238G/A polymorphisms, and the risk of autoimmune liver disease (AILD), yet the results are conflicting. To derive a more precise estimation of the relationship, we performed this meta-analysis. A systematic review was conducted to identify all eligible studies of TNF-α polymorphisms and AILD risk. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association between the two TNF-α polymorphisms and AILD risk. A total of 15 eligible studies were identified. Overall, positive associations of -308G/A polymorphism with AILD risk were found (A vs G allele: OR =1.45, 95%CI = 1.13- 1.86; AA vs GG: OR = 2.74, 95%CI = 1.51- 4.96; GA vs GG: OR = 1.46, 95%CI = 1.11- 1.92;dominant model: OR = 1.57, 95%CI = 1.18- 2.10; recessive model: OR = 2.22, 95%CI = 1.31- 3.76). In subgroup analysis by ethnicity, a significantly higher risk was found in Caucasians. In subgroup analysis by AILD category, significant association was observed in autoimmune hepatitis and primary sclerosing cholangitis, especially in Caucasians. Patients carrying TNF-α-238A allele had a slightly decreased risk of developing AILD (OR = 0.65, 95%CI = 0.48- 0.87). However, we found both TNF-α polymorphisms were not associated with primary biliary cirrhosis risk, even in subgroup analysis. Our meta-analysis suggests that the TNF-α-308G/A and -238G/A polymorphisms may contribute to AILD susceptibility in Caucasians,especially for autoimmune hepatitis and primary sclerosing cholangitis. Nevertheless, we found both TNF-α polymorphisms were unlikely to be associated with the risk of primary biliary cirrhosis