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Autoimmune hepatitis (AIH) is an autoimmune liver disease and cirrhosis is sometimes complicated with AIH at diagnosis, influencing its prognosis.  TNFAIP3  gene encodes A20, an inhibitor of nuclear factor-κB pathway, and is a susceptibility gene for autoimmune diseases. We investigated deleterious variants in the coding regions of  TNFAIP3  gene of Japanese AIH patients or those with cirrhosis. The deleterious variants in the coding regions of  TNFAIP3  gene were analyzed by the cycle sequencing method and the frequencies of deleterious  TNFAIP3  alleles of AIH or AIH with cirrhosis were compared with those of Japanese controls. The deleterious alleles in  TNFAIP3  were not associated with AIH. A significant association was shown for the deleterious alleles in  TNFAIP3  ( P  = 0.0180, odds ratio (OR) 4.28, 95% confidence interval (CI) 1.53–11.95) with AIH with cirrhosis at presentation. The serum IgM levels in AIH patients with deleterious alleles in  TNFAIP3  were tended to be lower than those without ( P  = 0.0152,  Q  = 0.1216). The frequency of deleterious alleles in  TNFAIP3  was higher in the AIH subset without the  DRB1  risk alleles than that with ( P  = 0.0052, OR 5.10, 95%CI 1.55–16.74). The deleterious alleles in  TNFAIP3 were associated with AIH with cirrhosis.

Role of deleterious single nucleotide variants in the coding regions of TNFAIP3 for Japanese autoimmune hepatitis with cirrhosis