Publicación Artículo científico (article). 2022

A Very Rare Variant in SREBF2, a Possible Cause of Hypercholesterolemia and Increased Glycemic Levels

Digital.CSIC. Repositorio Institucional del CSIC
Digital.CSIC. Repositorio Institucional del CSIC
  • García-García, Ana-Barbara
  • Martinez-Hervás, Sergio
  • Vernia, Santiago
  • Ivorra, Carmen
  • Pulido, Ines
  • Martin-Escudero, Juan-Carlos
  • Casado, Marta
  • Carretero, Julián
  • Real, Jose T.
  • Chaves, Felipe Javier
10 páginas, 2 figuras, 2 tablas. This article belongs to the Special Issue Molecular Research of Genes Involved in Metabolic Diseases. The following supporting information can be downloaded at: https: //, Figure S1: Comparison of the c.- 405A>G position in SREBF2 gene in five Hominidae species; Table S1: Sequences of primers used in this work., Patients with high cholesterol and glucose levels are at high risk for cardiovascular disease. The Sterol Regulatory Element Binding Protein (SREBP) system regulates genes involved in lipid, cholesterol and glucose pathways. Autosomal Dominant Hypercholesterolemias (ADHs) are a group of diseases with increased cholesterol levels. They affect 1 out of every 500 individuals. About 20-30% of patients do not present any mutation in the known genes (LDLR, APOB and PCSK9). ADHs constitute a good model to identify the genes involved in the alteration of lipid levels or possible therapeutic targets. In this paper, we studied whether a mutation in the SREBP system could be responsible for ADH and other metabolic alterations present in these patients. Forty-one ADH patients without mutations in the main responsible genes were screened by direct sequencing of SREBP system genes. A luciferase reporter assay of the found mutation and an oral glucose tolerance test in carriers and non-carriers were performed. We found a novel mutation in the SREBF2 gene that increases transcription levels and cosegregates with hypercholesterolemia, and we found increased glucose levels in one family. SREBP2 is known to be involved in cholesterol synthesis, plasma levels and glucose metabolism in humans. The found mutation may involve the SREBF2 gene in hypercholesterolemia combined with hyperglycemia., This work was funded by the CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM, which is an initiative of the Instituto de Salud Carlos III, Madrid, Spain), research grants PI17/0497 and PI21/00506 from FIS to F.J.C., grant AP11-091 from Generalitat Valenciana to F.J.C. and grant PID2019-108977RB-I00 from the Spanish Ministry of Science and Innovation to M.C., Peer reviewed

Digital.CSIC. Repositorio Institucional del CSIC

Digital.CSIC. Repositorio Institucional del CSIC
Ver en:
Digital.CSIC. Repositorio Institucional del CSIC