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Teo K, Abeysekera KWM, Adams L, et al. rs641738C>T near MBOAT7 is associated with liver fat, ALT and fibrosis in NAFLD: A meta-analysis. J Hepatol. 2020;74(1):20-30doi: 10.1016/j.jhep.2020.08.027.
Teo, K., Abeysekera, K. W. M., Adams, L., Aigner, E., Anstee, Q. M., Banales, J. M., Banerjee, R., Basu, P., Berg, T., Bhatnagar, P., Buch, S., Canbay, A., Caprio, S., Chatterjee, A., Ida Chen, Y. D., Chowdhury, A., Daly, A. K., Datz, C., de Gracia Hahn, D., DiStefano, J. K., Dong, J., Duret, A., Emdin, C., Fairey, M., Gerhard, G. S., Guo, X., Hampe, J., Hickman, M., Heintz, L., Hudert, C., Hunter, H., Kelly, M., Kozlitina, J., Krawczyk, M., Lammert, F., Langenberg, C., Lavine, J., Li, L., Lim, H. K., Loomba, R., Luukkonen, P. K., Melton, P. E., Mori, T. A., Palmer, N. D., Parisinos, C. A., Pillai, S. G., Qayyum, F., Reichert, M. C., Romeo, S., Rotter, J. I., Im, Y. R., Santoro, N., Schafmayer, C., Speliotes, E. K., Stender, S., Stickel, F., Still, C. D., Strnad, P., Taylor, K. D., Tybjærg-Hansen, A., Umano, G. R., Utukuri, M., Valenti, L., Wagenknecht, L. E., Wareham, N. J., Watanabe, R. M., Wattacheril, J., Yaghootkar, H., Yki-Järvinen, H., Young, K. A., & Mann, J. P. (2021). rs641738C>T near MBOAT7 is associated with liver fat, ALT and fibrosis in NAFLD: A meta-analysis. Journal of hepatology, 74(1), 20-30. https://doi.org/10.1016/j.jhep.2020.08.027
Teo, Kevin, et al. "rs641738C>T near MBOAT7 is associated with liver fat, ALT and fibrosis in NAFLD: A meta-analysis." Journal of hepatology vol. 74,1 (2021): 20-30. doi: https://doi.org/10.1016/j.jhep.2020.08.027
Teo K, Abeysekera KWM, Adams L, Aigner E, Anstee QM, Banales JM, Banerjee R, Basu P, Berg T, Bhatnagar P, Buch S, Canbay A, Caprio S, Chatterjee A, Ida Chen YD, Chowdhury A, Daly AK, Datz C, de Gracia Hahn D, DiStefano JK, Dong J, Duret A, Emdin C, Fairey M, Gerhard GS, Guo X, Hampe J, Hickman M, Heintz L, Hudert C, Hunter H, Kelly M, Kozlitina J, Krawczyk M, Lammert F, Langenberg C, Lavine J, Li L, Lim HK, Loomba R, Luukkonen PK, Melton PE, Mori TA, Palmer ND, Parisinos CA, Pillai SG, Qayyum F, Reichert MC, Romeo S, Rotter JI, Im YR, Santoro N, Schafmayer C, Speliotes EK, Stender S, Stickel F, Still CD, Strnad P, Taylor KD, Tybjærg-Hansen A, Umano GR, Utukuri M, Valenti L, Wagenknecht LE, Wareham NJ, Watanabe RM, Wattacheril J, Yaghootkar H, Yki-Järvinen H, Young KA, Mann JP. rs641738C>T near MBOAT7 is associated with liver fat, ALT and fibrosis in NAFLD: A meta-analysis. J Hepatol. 2021 Jan;74(1):20-30. doi: 10.1016/j.jhep.2020.08.027. Epub 2020 Aug 31. PMID: 32882372; PMCID: PMC7755037.
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J Hepatol. 2021 Jan;74(1):20-30. doi: 10.1016/j.jhep.2020.08.027. Epub 2020 Aug 31.

rs641738C>T near MBOAT7 is associated with liver fat, ALT and fibrosis in NAFLD: A meta-analysis.

Journal of hepatology

Kevin Teo, Kushala W M Abeysekera, Leon Adams, Elmar Aigner, Quentin M Anstee, Jesus M Banales, Rajarshi Banerjee, Priyadarshi Basu, Thomas Berg, Pallav Bhatnagar, Stephan Buch, Ali Canbay, Sonia Caprio, Ankita Chatterjee, Yii-Der Ida Chen, Abhijit Chowdhury, Ann K Daly, Christian Datz, Dana de Gracia Hahn, Johanna K DiStefano, Jiawen Dong, Amedine Duret, Connor Emdin, Madison Fairey, Glenn S Gerhard, Xiuqing Guo, Jochen Hampe, Matthew Hickman, Lena Heintz, Christian Hudert, Harriet Hunter, Matt Kelly, Julia Kozlitina, Marcin Krawczyk, Frank Lammert, Claudia Langenberg, Joel Lavine, Lin Li, Hong Kai Lim, Rohit Loomba, Panu K Luukkonen, Phillip E Melton, Trevor A Mori, Nicholette D Palmer, Constantinos A Parisinos, Sreekumar G Pillai, Faiza Qayyum, Matthias C Reichert, Stefano Romeo, Jerome I Rotter, Yu Ri Im, Nicola Santoro, Clemens Schafmayer, Elizabeth K Speliotes, Stefan Stender, Felix Stickel, Christopher D Still, Pavel Strnad, Kent D Taylor, Anne Tybjærg-Hansen, Giuseppina Rosaria Umano, Mrudula Utukuri, Luca Valenti, Lynne E Wagenknecht, Nicholas J Wareham, Richard M Watanabe, Julia Wattacheril, Hanieh Yaghootkar, Hannele Yki-Järvinen, Kendra A Young, Jake P Mann

Affiliations

  1. School of Clinical Medicine, University of Cambridge, Cambridge, UK.
  2. MRC Integrative Epidemiology Unit (IEU), University of Bristol, Bristol, UK.
  3. Medical School, Faculty of Health and Medical Sciences, University of Western Australia, Perth, WA, Australia; Department of Hepatology, Sir Charles Gairdner Hospital, Perth, WA, Australia.
  4. First Department of Medicine, Paracelsus Medical University Salzburg, Austria.
  5. Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK; Newcastle NIHR Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
  6. Department on Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), CIBERehd, Ikerbasque, San Sebastian, Spain.
  7. Perspectum Ltd, Oxford, UK.
  8. National Institute of Biomedical Genomics, Kalyani, India.
  9. Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany.
  10. Eli Lilly and Company, Indianapolis, IN, USA.
  11. Medical Department 1, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany.
  12. Gastroenterology, Hepatology and Infectiology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
  13. Yale University, Department of Pediatrics, New Haven, CT, USA.
  14. The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
  15. Institute of Post Graduate Medical Education and Research, Kolkata, India.
  16. Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
  17. Department of Internal Medicine, General Hospital Oberndorf, Teaching Hospital of the Paracelsus Medical University Salzburg, Oberndorf, Austria.
  18. Diabetes and Fibrotic Disease Unit Translational Genomics Research Institute (TGen), Phoenix, AZ, USA.
  19. Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Boston, MA, USA.
  20. Department of Medical Genetics and Molecular Biochemistry, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA.
  21. Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany.
  22. Department of Pediatric Gastroenterology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
  23. Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  24. Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany; Laboratory of Metabolic Liver Diseases, Department of General, Transplant and Liver Surgery, Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland.
  25. MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
  26. Department of Pediatrics, Columbia University, New York, NY, USA.
  27. BioStat Solutions LLC, Frederick, MD, USA.
  28. NAFLD Research Center, Division of Gastroenterology and Epidemiology, University of California at San Diego, La Jolla, CA, USA.
  29. Minerva Foundation Institute for Medical Research, Helsinki, Finland; Department of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Yale University School of Medicine, New Haven, CT, USA.
  30. School of Global Population Health, Faculty of Health and Medical Sciences, The University of Western Australia, Perth, WA, Australia; School of Pharmacy and Biomedical Sciences, Faculty of Health Sciences, Curtin University, Perth, WA, Australia; Menzies Institute for Medical Research, College of Health and Medicine, University of Tasmania, Hobart, Australia.
  31. Medical School, Faculty of Health and Medical Sciences, University of Western Australia, Perth, WA, Australia.
  32. Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA.
  33. Institute of Health Informatics, Faculty of Population Health Sciences, University College London, London, UK.
  34. Department of Clinical Biochemistry, Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark.
  35. Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden; Cardiology Department, Sahlgrenska University Hospital, Gothenburg, Sweden; Clinical Nutrition Unit, Department of Medical and Surgical Sciences, University Magna Graecia, Catanzaro, Italy.
  36. Yale University, Department of Pediatrics, New Haven, CT, USA; Department of Medicine and Health Sciences 'V. Tiberio' University of Molise, Campobasso, Italy.
  37. Department of Visceral and Thoracic Surgery, Kiel University, Kiel, Germany.
  38. Division of Gastroenterology and Hepatology, Department of Medicine, University of Michigan Health System, Ann Arbor, MI, USA; Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI, USA.
  39. Department of Gastroenterology and Hepatology, University Hospital of Zurich, Zurich, Switzerland.
  40. Geisinger Obesity Institute, Danville, PA, USA.
  41. Medical Clinic III, University Hospital RWTH Aachen, Aachen, Germany.
  42. Yale University, Department of Pediatrics, New Haven, CT, USA; Department of the Woman, the Child, of General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples, Italy.
  43. Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy; Translational Medicine, Department of Transfusion Medicine and Hematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Milan, Italy.
  44. Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA.
  45. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  46. Department of Medicine, Center for Liver Disease and Transplantation, Columbia University College of Physicians and Surgeons, New York Presbyterian Hospital, New York, NY, USA.
  47. Genetics of Complex Traits, College of Medicine and Health, University of Exeter, Exeter, UK.
  48. Minerva Foundation Institute for Medical Research, Helsinki, Finland; Department of Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
  49. Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, CO, USA.
  50. MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK. Electronic address: [email protected].

PMID: 32882372 PMCID: PMC7755037 DOI: 10.1016/j.jhep.2020.08.027

Abstract

BACKGROUND & AIMS: A common genetic variant near MBOAT7 (rs641738C>T) has been previously associated with hepatic fat and advanced histology in NAFLD; however, these findings have not been consistently replicated in the literature. We aimed to establish whether rs641738C>T is a risk factor across the spectrum of NAFLD and to characterise its role in the regulation of related metabolic phenotypes through a meta-analysis.

METHODS: We performed a meta-analysis of studies with data on the association between rs641738C>T genotype and liver fat, NAFLD histology, and serum alanine aminotransferase (ALT), lipids or insulin. These included directly genotyped studies and population-level data from genome-wide association studies (GWAS). We performed a random effects meta-analysis using recessive, additive and dominant genetic models.

RESULTS: Data from 1,066,175 participants (9,688 with liver biopsies) across 42 studies were included in the meta-analysis. rs641738C>T was associated with higher liver fat on CT/MRI (+0.03 standard deviations [95% CI 0.02-0.05], p

CONCLUSIONS: Our study validates rs641738C>T near MBOAT7 as a risk factor for the presence and severity of NAFLD in individuals of European descent.

LAY SUMMARY: Fatty liver disease is a common condition where fat builds up in the liver, which can cause liver inflammation and scarring (including 'cirrhosis'). It is closely linked to obesity and diabetes, but some genes are also thought to be important. We did this study to see whether one specific change ('variant') in one gene ('MBOAT7') was linked to fatty liver disease. We took data from over 40 published studies and found that this variant near MBOAT7 is linked to more severe fatty liver disease. This means that drugs designed to work on MBOAT7 could be useful for treating fatty liver disease.

Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Keywords: ALSPAC; Diabetes; Fibrosis; MBOAT7; NAFLD; Triglyceride

Conflict of interest statement

Conflict of interest C.E. reports receiving personal fees from Navitor Pharma and Novartis. The other authors declare no conflicts of interest that pertain to this work. Please refer to the accompanyi

References

  1. Sci Rep. 2018 Feb 27;8(1):3702 - PubMed
  2. J Hepatol. 2020 Sep;73(3):505-515 - PubMed
  3. Mol Biol Cell. 2012 Dec;23(24):4689-700 - PubMed
  4. Nature. 2020 May;581(7809):434-443 - PubMed
  5. Genes Cells. 2008 Aug;13(8):879-88 - PubMed
  6. Nat Genet. 2015 Dec;47(12):1443-8 - PubMed
  7. Liver Int. 2019 Mar;39(3):540-556 - PubMed
  8. Gastroenterology. 2020 Oct;159(4):1276-1289.e7 - PubMed
  9. PLoS One. 2018 Nov 26;13(11):e0207923 - PubMed
  10. Clin Gastroenterol Hepatol. 2020 Oct;18(11):2592-2599.e10 - PubMed
  11. Sci Rep. 2019 Mar 6;9(1):3682 - PubMed
  12. J Biomed Inform. 2009 Apr;42(2):377-81 - PubMed
  13. Sci Rep. 2018 Mar 23;8(1):5097 - PubMed
  14. Nat Genet. 2014 Jun;46(6):543-550 - PubMed
  15. PLoS Genet. 2011 Mar;7(3):e1001324 - PubMed
  16. J Lipid Res. 2017 Jan;58(1):247-255 - PubMed
  17. Gastroenterology. 2016 May;150(5):1219-1230.e6 - PubMed
  18. Hepatol Commun. 2018 Mar 23;2(5):561-570 - PubMed
  19. Hepatology. 2005 Jun;41(6):1313-21 - PubMed
  20. Sci Rep. 2017 Jul 3;7(1):4492 - PubMed
  21. N Engl J Med. 2018 Mar 22;378(12):1096-1106 - PubMed
  22. EBioMedicine. 2020 Feb;52:102658 - PubMed
  23. Am J Gastroenterol. 2018 Mar;113(3):376-383 - PubMed
  24. J Hepatol. 2016 Dec;65(6):1263-1265 - PubMed
  25. Bioinformatics. 2019 Nov 1;35(22):4851-4853 - PubMed
  26. Int J Epidemiol. 2013 Feb;42(1):111-27 - PubMed
  27. Hum Mol Genet. 2020 Dec 18;29(20):3451-3463 - PubMed
  28. Clin Res Hepatol Gastroenterol. 2020 Oct;44(5):646-652 - PubMed
  29. Hepatology. 2020 Jul;72(1):330-346 - PubMed
  30. Nat Genet. 2011 Oct 16;43(11):1131-8 - PubMed
  31. J Hepatol. 2020 Aug;73(2):241-251 - PubMed
  32. Hepatol Commun. 2019 Feb 11;3(4):587-596 - PubMed
  33. Elife. 2019 Oct 17;8: - PubMed
  34. Nat Commun. 2016 Sep 15;7:12757 - PubMed
  35. Liver Int. 2020 Feb;40(2):405-415 - PubMed
  36. Nat Genet. 2013 Jun;45(6):580-5 - PubMed
  37. Gut. 2021 Jan;70(1):180-193 - PubMed
  38. Am J Hum Genet. 2016 Oct 6;99(4):912-916 - PubMed
  39. PLoS Genet. 2020 Apr 13;16(4):e1008629 - PubMed
  40. Clin Gastroenterol Hepatol. 2020 Apr;18(4):935-944.e3 - PubMed
  41. Hepatology. 2014 Aug;60(2):565-75 - PubMed
  42. J Intern Med. 2018 Apr;283(4):356-370 - PubMed
  43. JAMA. 2000 Apr 19;283(15):2008-12 - PubMed
  44. Hepatology. 2017 Jun;65(6):1840-1850 - PubMed
  45. J Biol Chem. 2008 Oct 31;283(44):30235-45 - PubMed
  46. Nat Genet. 2018 Nov;50(11):1505-1513 - PubMed
  47. Nucleic Acids Res. 2017 Jan 4;45(D1):D896-D901 - PubMed
  48. J Gastroenterol Hepatol. 2018 Jun;33(6):1277-1285 - PubMed
  49. Clin Res Hepatol Gastroenterol. 2019 Oct;43(5):533-541 - PubMed
  50. Wellcome Open Res. 2019 Mar 14;4:51 - PubMed
  51. Bioinformatics. 2015 Apr 15;31(8):1334-6 - PubMed
  52. Eur J Clin Invest. 2020 Oct;50(10):e13331 - PubMed
  53. PLoS Biol. 2008 May 6;6(5):e107 - PubMed
  54. Cell Metab. 2020 Jan 7;31(1):35-45 - PubMed
  55. J Inherit Metab Dis. 2019 Mar;42(2):381-388 - PubMed
  56. PLoS One. 2018 Jan 31;13(1):e0185490 - PubMed

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