Hepatic steatosis and steatohepatitis: a functional meta-analysis of sex-based differences in transcriptomic studies

Biology of Sex Differences

Marta R. Hidalgo¹  Pablo Malmierca-Merlo²  José F. Català-Senent³  Francisco García-García³  María de la Iglesia-Vayá⁴  Gopanandan Parthasarathy⁵  Harmeet Malhi⁵  Marina Berenguer⁶ 

[1] Bioinformatics and Biostatistics Unit, Principe Felipe Research Center, Valencia, Spain;Bioinformatics and Biostatistics Unit, Principe Felipe Research Center, Valencia, Spain;Atos Research & Innovation (ARI), Madrid, Spain;Bioinformatics and Biostatistics Unit, Principe Felipe Research Center, Valencia, Spain;Spanish National Bioinformatics Institute, ELIXIR-Spain (INB, ELIXIR-ES), Madrid, Spain;Biomedical Imaging Unit FISABIO-CIPF, Fundación para el Fomento de la Investigación Sanitario y Biomédica de la Comunidad Valenciana, Valencia, Spain;Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA;Liver Transplantation and Hepatology Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain;Grupo de Hepatología, Cirugía HBP y Trasplantes, Instituto de Investigación Sanitaria La Fe, Valencia, Spain;CIBERehd, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid, Spain;Department of Medicine, Universitat de València, Valencia, Spain;

关键词: Non-alcoholic fatty liver disease;    Sex characteristics;    Precision medicine;    Computational biology;    Transcriptome profiling;   

DOI  :  10.1186/s13293-021-00368-1

来源: Springer

【 摘 要 】

BackgroundPrevious studies have described sex-based differences in the epidemiological and clinical patterns of non-alcoholic fatty liver disease (NAFLD); however, we understand relatively little regarding the underlying molecular mechanisms. Herein, we present the first systematic review and meta-analysis of NAFLD transcriptomic studies to identify sex-based differences in the molecular mechanisms involved during the steatosis (NAFL) and steatohepatitis (NASH) stages of the disease.MethodsTranscriptomic studies in the Gene Expression Omnibus database were systematically reviewed following the PRISMA statement guidelines. For each study, NAFL and NASH in premenopausal women and men were compared using a dual strategy: gene-set analysis and pathway activity analysis. Finally, the functional results of all studies were integrated into a meta-analysis.ResultsWe reviewed a total of 114 abstracts and analyzed seven studies that included 323 eligible patients. The meta-analyses identified significantly altered molecular mechanisms between premenopausal women and men, including the overrepresentation of genes associated with DNA regulation, vinculin binding, interleukin-2 responses, negative regulation of neuronal death, and the transport of ions and cations in premenopausal women. In men, we discovered the overrepresentation of genes associated with the negative regulation of interleukin-6 and the establishment of planar polarity involved in neural tube closure.ConclusionsOur meta-analysis of transcriptomic data provides a powerful approach to identify sex-based differences in NAFLD. We detected differences in relevant biological functions and molecular terms between premenopausal women and men. Differences in immune responsiveness between men and premenopausal women with NAFLD suggest that women possess a more immune tolerant milieu, while men display an impaired liver regenerative response.Graphical abstract

【 授权许可】

CC BY