Nonalcoholic steatohepatitis is associated with a state of betaine-insufficiency.
Nonalcoholic fatty liver disease (NAFLD) develops from a complex process, which includes changes in the liver methylome. Betaine plays a pivotal role in the regulation of methylogenesis. We performed a two-stage case-control study, which included patients with biopsy-proven NAFLD to explore circulating levels of betaine and its association with the histological spectrum. We also explored the association between a missense rs1805074, p.Ser646Pro variant in DMGDH (dimethylglycine dehydrogenase mitochondrial) and NAFLD severity (n=390).



In the discovery phase (n=48), betaine levels were associated with the disease severity (P=.0030), including liver inflammation (Spearman R:-0.51, P=.001), ballooning degeneration (R: -0.50, P=.01) and fibrosis (R: -0.54, P=.0008). Betaine levels were significantly decreased in nonalcoholic steatohepatitis (NASH) in comparison with nonalcoholic fatty liver (NAFL). Further replication (n=51) showed that betaine levels were associated with advanced NAFLD (P=.0085), and patients with NASH had a 1.26-fold decrease in betaine levels compared with those with NAFL. The rs1805074 was significantly associated with the disease severity (P=.011).



NAFLD severity is associated with a state of betaine-insufficiency.
Department of Clinical and Molecular Hepatology, Institute of Medical Research A Lanari-IDIM, University of Buenos Aires- National Scientific and Technical Research Council (CONICET), Ciudad Autónoma de Buenos Aires, Argentina.
Silvia
S
Sookoian
Department of Internal Medicine, Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
Puneet
P
Puri
Liver Unit, Medicine and Surgery Department, Hospital Abel Zubizarreta, Ciudad Autónoma de Buenos Aires, Argentina.
Gustavo O
GO
Castaño
Department of Clinical and Molecular Hepatology, Institute of Medical Research A Lanari-IDIM, University of Buenos Aires- National Scientific and Technical Research Council (CONICET), Ciudad Autónoma de Buenos Aires, Argentina.|Department of Molecular Genetics and Biology of Complex Diseases, Institute of Medical Research A Lanari-IDIM, University of Buenos Aires-National Scientific and Technical Research Council (CONICET), Ciudad Autónoma de Buenos Aires, Argentina.
Romina
R
Scian
Department of Internal Medicine, Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
Faridodin
F
Mirshahi
Department of Internal Medicine, Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
Arun J
AJ
Sanyal
Department of Molecular Genetics and Biology of Complex Diseases, Institute of Medical Research A Lanari-IDIM, University of Buenos Aires-National Scientific and Technical Research Council (CONICET), Ciudad Autónoma de Buenos Aires, Argentina.
Carlos J
CJ
Pirola
D000328:Adult; D001118:Argentina; D001622:Betaine / Q000097:blood*; D015415:Biomarkers; D016022:Case-Control Studies; D050893:Dimethylglycine Dehydrogenase / Q000235:genetics*; D018450:Disease Progression; D005234:Fatty Liver / Q000473:pathology; D005260:Female; D005355:Fibrosis; D006801:Humans; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics*; D020125:Mutation, Missense; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood* / Q000235:genetics* / Q000473:pathology; D012044:Regression Analysis; D012720:Severity of Illness Index
D015415:Biomarkers; D024101:Mitochondrial Proteins; D001622:Betaine; C494398:DMGDH protein, human; D050893:Dimethylglycine Dehydrogenase
DNA methylation; betaine; biomarkers; dimethylglycine dehydrogenase mitochondrial; epigenetics; fibrosis; genetics; inflammation; metabolomics; nonalcoholic fatty liver disease; nonalcoholic steatohepatitis