SMIM1 absence is associated with reduced energy expenditure and excess weight.

Autor:	Stefanucci L; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK; National Health Service (NHS) Blood and Transplant, Cambridge Biomedical Campus, Cambridge, UK; British Heart Foundation, Cambridge Centre for Research Excellence, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK., Moslemi C; Department of Clinical Immunology, Zealand University Hospital (Roskilde University), Køge, Denmark., Tomé AR; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK; National Health Service (NHS) Blood and Transplant, Cambridge Biomedical Campus, Cambridge, UK., Virtue S; Wellcome-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK., Bidault G; University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, MDU MRC, Addenbrooke's Hospital, Cambridge, UK., Gleadall NS; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK; National Health Service (NHS) Blood and Transplant, Cambridge Biomedical Campus, Cambridge, UK., Watson LPE; NIHR Cambridge Clinical Research Facility, Cambridge University Hospitals, Cambridge Biomedical Campus, Cambridge, UK., Kwa JE; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK., Burden F; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK; National Health Service (NHS) Blood and Transplant, Cambridge Biomedical Campus, Cambridge, UK., Farrow S; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK; National Health Service (NHS) Blood and Transplant, Cambridge Biomedical Campus, Cambridge, UK., Chen J; Department of Clinical and Biomedical Sciences, University of Exeter Medical School, Faculty of Health and Life Sciences RILD Building, Barrack Road, Exeter, UK., Võsa U; Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia., Burling K; NIHR Cambridge Biomedical Research Centre Core Biochemical Assay Laboratory, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Walker L; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK; National Health Service (NHS) Blood and Transplant, Cambridge Biomedical Campus, Cambridge, UK., Ord J; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK; National Health Service (NHS) Blood and Transplant, Cambridge Biomedical Campus, Cambridge, UK., Barker P; NIHR Cambridge Biomedical Research Centre Core Biochemical Assay Laboratory, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Warner J; Wellcome-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK., Frary A; NIHR National BioResource, Cambridge University Hospitals NHS Foundation, Cambridge Biomedical Campus, Cambridge, UK., Renhstrom K; NIHR National BioResource, Cambridge University Hospitals NHS Foundation, Cambridge Biomedical Campus, Cambridge, UK., Ashford SE; NIHR National BioResource, Cambridge University Hospitals NHS Foundation, Cambridge Biomedical Campus, Cambridge, UK., Piper J; NIHR Cambridge Clinical Research Facility, Cambridge University Hospitals, Cambridge Biomedical Campus, Cambridge, UK., Biggs G; NIHR Cambridge Clinical Research Facility, Cambridge University Hospitals, Cambridge Biomedical Campus, Cambridge, UK., Erber WN; Discipline of Pathology and Laboratory Science, School of Biomedical Sciences, The University of Western Australia, Perth, WA, Australia., Hoffman GJ; Discipline of Pathology and Laboratory Medicine, Medical School, The University of Western Australia, Perth, WA, Australia., Schoenmakers N; Wellcome-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK., Erikstrup C; Department of Clinical Immunology, Aarhus University Hospital, Aarhus University, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark., Rieneck K; Department of Clinical Immunology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark., Dziegiel MH; Department of Clinical Immunology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark., Ullum H; Statens Serum Institut, Copenhagen, Denmark., Azzu V; Wellcome-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK; Department of Gastroenterology, Norfolk & Norwich University Hospitals NHS Foundation Trust, Norwich, UK., Vacca M; Wellcome-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK; Interdisciplinary Department of Medicine, Università degli Studi di Bari 'Aldo Moro', Bari, Italy; Roger Williams Institute of Hepatology, London, UK., Aparicio HJ; Department of Neurology, Boston University School of Medicine, Boston, MA, USA., Hui Q; Atlanta VA Medical Center, Decatur, GA, USA; Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA, USA., Cho K; Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA, USA; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Sun YV; Atlanta VA Medical Center, Decatur, GA, USA; Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA, USA., Wilson PW; Atlanta VA Medical Center, Decatur, GA, USA; Emory University Schools of Medicine and Public Health, Atlanta, GA, USA., Bayraktar OA; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK., Vidal-Puig A; University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, MDU MRC, Addenbrooke's Hospital, Cambridge, UK; Centro de Innvestigacion Principe Felipe, Valencia, Spain., Ostrowski SR; Department of Clinical Immunology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark., Astle WJ; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK; National Health Service (NHS) Blood and Transplant, Cambridge Biomedical Campus, Cambridge, UK; British Heart Foundation, Cambridge Centre for Research Excellence, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK; MRC Biostatistics Unit, East Forvie Building, Cambridge Biomedical Campus, University of Cambridge, Cambridge, UK., Olsson ML; Clinical Immunology and Transfusion Medicine, Office for Medical Services, Region Skåne, Lund, Sweden; Department of Laboratory Medicine, Division of Hematology and Transfusion Medicine, Lund University, Lund, Sweden., Storry JR; Clinical Immunology and Transfusion Medicine, Office for Medical Services, Region Skåne, Lund, Sweden; Department of Laboratory Medicine, Division of Hematology and Transfusion Medicine, Lund University, Lund, Sweden., Pedersen OB; Department of Clinical Immunology, Zealand University Hospital (Roskilde University), Køge, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark., Ouwehand WH; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK; National Health Service (NHS) Blood and Transplant, Cambridge Biomedical Campus, Cambridge, UK; Department of Haematology, Cambridge University Hospitals NHS Trust, CB2 0QQ Cambridge, UK; Department of Haematology, University College London Hospitals NHS Trust, NW1 2BU London, UK., Chatterjee K; Wellcome-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK., Vuckovic D; Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine, Imperial College London, London, UK., Frontini M; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK; National Health Service (NHS) Blood and Transplant, Cambridge Biomedical Campus, Cambridge, UK; British Heart Foundation, Cambridge Centre for Research Excellence, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK; Department of Clinical and Biomedical Sciences, University of Exeter Medical School, Faculty of Health and Life Sciences RILD Building, Barrack Road, Exeter, UK. Electronic address: m.frontini@exeter.ac.uk.
Jazyk:	angličtina
Zdroj:	Med (New York, N.Y.) [Med] 2024 Sep 13; Vol. 5 (9), pp. 1083-1095.e6. Date of Electronic Publication: 2024 Jun 20.
DOI:	10.1016/j.medj.2024.05.015
Abstrakt:	Background: Obesity rates have nearly tripled in the past 50 years, and by 2030 more than 1 billion individuals worldwide are projected to be obese. This creates a significant economic strain due to the associated non-communicable diseases. The root cause is an energy expenditure imbalance, owing to an interplay of lifestyle, environmental, and genetic factors. Obesity has a polygenic genetic architecture; however, single genetic variants with large effect size are etiological in a minority of cases. These variants allowed the discovery of novel genes and biology relevant to weight regulation and ultimately led to the development of novel specific treatments. Methods: We used a case-control approach to determine metabolic differences between individuals homozygous for a loss-of-function genetic variant in the small integral membrane protein 1 (SMIM1) and the general population, leveraging data from five cohorts. Metabolic characterization of SMIM1 -/- individuals was performed using plasma biochemistry, calorimetric chamber, and DXA scan. Findings: We found that individuals homozygous for a loss-of-function genetic variant in SMIM1 gene, underlying the blood group Vel, display excess body weight, dyslipidemia, altered leptin to adiponectin ratio, increased liver enzymes, and lower thyroid hormone levels. This was accompanied by a reduction in resting energy expenditure. Conclusion: This research identified a novel genetic predisposition to being overweight or obese. It highlights the need to investigate the genetic causes of obesity to select the most appropriate treatment given the large cost disparity between them. Funding: This work was funded by the National Institute of Health Research, British Heart Foundation, and NHS Blood and Transplant. Competing Interests: Declaration of interests J.S. is the deputy CEO and 50% owner of BLUsang AB. He holds patents on Vel genotyping (inventors: Jill Storry, Magnus Jöud, Björn Nilsson, and Martin L. Olsson). J.S. has received speaker fees, royalties, and honoraria from the following companies: Grifols Diagnostic Solutions, QuidelOrtho Inc., and Biorad Laboratories. J.S. receives an honorarium for Section Editor work, Vox Sanguinis from John Wiley & Sons Ltd. J.S. is Vice President of the International Society of Blood Transfusion and married to Professor M.L.O. M.L.O. is CEO and 50% owner of BLUsang AB. M.L.O. holds patents on Vel genotyping (inventors: Jill Storry, Magnus Jöud, Björn Nilsson, and Martin L. Olsson). M.L.O. received speaker fees, royalties, and honoraria from the following companies: Grifols Diagnostic Solutions, QuidelOrtho Inc., and Biorad Laboratories. M.L.O. is married to Adjunct Professor J.S. W.N.E. is chair of the International Council for Standardization in Haematology. W.N.E. works as advisor for Scorpio Labs and is on the editorial board of the Journal of Clinical Pathology. W.H.O. is chair of the Blood Transfusion Genomics Consortium. W.H.O. is in receipt of an educational/research grant from Thermo Fisher Scientific. N.G. offers scientific consulting services to Thermo Fisher Scientific. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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