Genetic and functional analyses of CTBP2 in anorexia nervosa and body weight regulation

The C-terminal binding protein 2 (CTBP2) gene (translational isoforms: CTBP2-L/S, RIBEYE) had been identified by a cross-trait analysis of genome-wide association studies for anorexia nervosa (AN) and body mass index (BMI). Here, we did a mutation analysis in CTBP2 by performing polymerase chain reactions with subsequent Sanger-sequencing to identify variants relevant for AN and body weight regulation and ensued functional studies. Analysis of the coding regions of CTBP2 in 462 female patients with AN (acute or recovered), 490 children and adolescents with severe obesity, 445 healthy-lean adult individuals and 168 healthy adult individuals with normal body weight detected 24 variants located in the specific exon of RIBEYE. In the initial analysis, three of these were rare non-synonymous variants (NSVs) detected heterozygously in patients with AN (p.Arg72Trp - rs146900874; p.Val289Met -rs375685611 and p.Gly362Arg - rs202010294). Four NSVs and one heterozygous frameshift variant were exclusively detected in children and adolescents with severe obesity (p.Pro53Ser - rs150867595; p.Gln175ArgfsTer45 - rs141864737; p.Leu310Val - rs769811964; p.Pro397Ala - rs76134089 and p.Pro402Ser - rs113477585). Ribeye mRNA was detected in mouse hypothalamus. No effect of fasting or overfeeding on murine hypothalamic Ribeye expression was determined. Yet, increased Ribeye expression was detected in hypothalami of leptin-treated Lep<sup>ob/ob</sup> mice. This increase was not related to reduced food intake and leptin-induced weight loss. We detected rare and frequent variants in the RIBEYE specific exon in both patients with AN and in children and adolescents with severe obesity. Our data suggest RIBEYE as a relevant gene for weight regulation.

Authors

Institutions

Publication Details

Journal
Molecular Psychiatry
Published
2024-11-07
DOI
https://doi.org/10.1038/s41380-024-02791-3
Citations
3
Primary Topic
Adipose Tissue and Metabolism
Type
article
Field-Weighted Citation Impact
0.98

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Genetic and functional analyses of CTBP2 in anorexia nervosa and body weight regulation

Stefan Ehrlich, Anke Hinney, Soni Shankhwar, Katrin Elisabeth Giel et al.
3 citations
Molecular Psychiatry
Adipose Tissue and Metabolism
0.98
article

Genetic and functional analyses of CTBP2 in anorexia nervosa and body weight regulation

Stefan Ehrlich, Anke Hinney, Soni Shankhwar, Katrin Elisabeth Giel, Beate Herpertz‐Dahlmann, Sigrid Jall, Yiran Zheng, Triinu Peters, Luisa Sophie Rajcsanyi, Martina de Zwaan, Simone Renner, Nirup K. Kurapati, Katrin Marcus, Roland Burghardt, Wolfgang Herzog, Stephan Zipfel, Kathy Keyvani, Timo D. Müller, Amrita Mukherjee, Johanna Giuranna, Jochen Seitz, Karin Egberts, Frank Schmitz, Manuel Föcker, Caroline May, M. Brandt
article en
3 citations

Abstract

The C-terminal binding protein 2 (CTBP2) gene (translational isoforms: CTBP2-L/S, RIBEYE) had been identified by a cross-trait analysis of genome-wide association studies for anorexia nervosa (AN) and body mass index (BMI). Here, we did a mutation analysis in CTBP2 by performing polymerase chain reactions with subsequent Sanger-sequencing to identify variants relevant for AN and body weight regulation and ensued functional studies. Analysis of the coding regions of CTBP2 in 462 female patients with AN (acute or recovered), 490 children and adolescents with severe obesity, 445 healthy-lean adult individuals and 168 healthy adult individuals with normal body weight detected 24 variants located in the specific exon of RIBEYE. In the initial analysis, three of these were rare non-synonymous variants (NSVs) detected heterozygously in patients with AN (p.Arg72Trp - rs146900874; p.Val289Met -rs375685611 and p.Gly362Arg - rs202010294). Four NSVs and one heterozygous frameshift variant were exclusively detected in children and adolescents with severe obesity (p.Pro53Ser - rs150867595; p.Gln175ArgfsTer45 - rs141864737; p.Leu310Val - rs769811964; p.Pro397Ala - rs76134089 and p.Pro402Ser - rs113477585). Ribeye mRNA was detected in mouse hypothalamus. No effect of fasting or overfeeding on murine hypothalamic Ribeye expression was determined. Yet, increased Ribeye expression was detected in hypothalami of leptin-treated Lep<sup>ob/ob</sup> mice. This increase was not related to reduced food intake and leptin-induced weight loss. We detected rare and frequent variants in the RIBEYE specific exon in both patients with AN and in children and adolescents with severe obesity. Our data suggest RIBEYE as a relevant gene for weight regulation.

Molecular PsychiatryVol. 30(5)
Heidelberg University (DE), University of Würzburg (DE), Helmholtz Zentrum München (DE), Medizinische Hochschule Hannover (DE), University Hospital Münster (DE), Essen University Hospital (DE), Lead Discovery Center (Germany) (DE), LWL-Universitätsklinik Hamm (DE), Deutsches Diabetes-Zentrum e.V. (DE), German Center for Diabetes Research (DE), Heinrich Heine University Düsseldorf (DE), University of Duisburg-Essen (DE), Technische Universität Dresden (DE), Ludwig-Maximilians-Universität München (DE), RWTH Aachen University (DE), Ruhr University Bochum (DE), Saarland University (DE)
European Commission, Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, Universität Duisburg-Essen
Good health and well-being
Openalex Percentile: Top 23%
Adipose Tissue and Metabolism
0.98
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.