Silvia Sookoian1, Puneet Puri2, Gustavo O Castaño3, Romina Scian1,4, Faridodin Mirshahi2, Arun J Sanyal2, Carlos J Pirola4. 1. 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. 2. Department of Internal Medicine, Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University School of Medicine, Richmond, VA, USA. 3. Liver Unit, Medicine and Surgery Department, Hospital Abel Zubizarreta, Ciudad Autónoma de Buenos Aires, Argentina. 4. 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.
Abstract
BACKGROUND AND AIMS: 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). RESULTS: 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). CONCLUSION: NAFLD severity is associated with a state of betaine-insufficiency.
BACKGROUND AND AIMS: 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). RESULTS: 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). CONCLUSION: NAFLD severity is associated with a state of betaine-insufficiency.
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Authors: P León-Mimila; H Villamil-Ramírez; X S Li; D M Shih; S T Hui; E Ocampo-Medina; B López-Contreras; S Morán-Ramos; M Olivares-Arevalo; P Grandini-Rosales; L Macías-Kauffer; I González-González; R Hernández-Pando; F Gómez-Pérez; F Campos-Pérez; C Aguilar-Salinas; E Larrieta-Carrasco; T Villarreal-Molina; Z Wang; A J Lusis; S L Hazen; A Huertas-Vazquez; S Canizales-Quinteros Journal: Diabetes Metab Date: 2020-08-10 Impact factor: 6.041