Dataset Information

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

ABSTRACT: 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-?B 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 TNFAIP3were associated with AIH with cirrhosis.

SUBMITTER: Higuchi T

PROVIDER: S-EPMC6538649 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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

Higuchi Takashi T Oka Shomi S Furukawa Hiroshi H Nakamura Minoru M Komori Atsumasa A Abiru Seigo S Hashimoto Satoru S Shimada Masaaki M Yoshizawa Kaname K Kouno Hiroshi H Naganuma Atsushi A Ario Keisuke K Kaneyoshi Toshihiko T Yamashita Haruhiro H Takahashi Hironao H Makita Fujio F Yatsuhashi Hiroshi H Ohira Hiromasa H Migita Kiyoshi K

Scientific reports 20190528 1

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 meth ...[more]

PMID: 31138864

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Project description:Objectives: Autoimmune hepatitis (AIH) can progress into severe outcomes, i.e., decompensated cirrhosis, from remarkable and persistent inflammation in the liver. Considering the energy-expending nature of inflammation, we tried to define the metabolomics signatures of AIH to uncover the underlying mechanisms of cirrhosis development and its metabolic biomarkers. Methods: Untargeted metabolomics analysis was performed on sera samples from 79 AIH patients at the stages (phenotypes) of non-cirrhosis (n = 27), compensated cirrhosis (n = 22), and decompensated cirrhosis (n = 30). Pattern recognition was used to find unique metabolite fingerprints of cirrhosis with or without decompensation. Results: Out of the 294 annotated metabolites identified, 2 metabolic fingerprints were found associated with the development of cirrhosis (independent of the decompensated state, 42 metabolites) and the evolution of decompensated cirrhosis (out of 47 metabolites), respectively. The cirrhosis-associated fingerprints (eigenmetabolite) showed better capability to differentiate cirrhosis from non-cirrhosis patients than the aminotransferase-to-platelet ratio index. From the metabolic fingerprints, we found two pairs of metabolites (Mesobilirubinogen/6-Hydroxynicotinic acid and LysoPA(8:0/0:0)/7alpha-Hydroxycholesterol) calculated as ratio of intensities, which revealed robust abilities to identify cirrhosis or predict decompensated patients, respectively. These phenotype-related fingerprint metabolites featured fundamental energy supply disturbance along with the development of AIH cirrhosis and progression to decompensation, which was characterized as increased lipolysis, enhanced proteolysis, and increased glycolysis. Conclusions: Remodeling of metabolism to meet the liver inflammation-related energy supply is one of the key signatures of AIH in the development of cirrhosis and decompensation. Therefore, drug regulation metabolism has great potential in the treatment of AIH.

Dataset Information

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

Publications

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

Similar Datasets

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