Forskning
Udskriv Udskriv
Switch language
Rigshospitalet - en del af Københavns Universitetshospital
Udgivet

Genetic inactivation of ANGPTL4 improves glucose homeostasis and is associated with reduced risk of diabetes

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Whole genome landscapes of uveal melanoma show an ultraviolet radiation signature in iris tumours

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Genomic analysis of male puberty timing highlights shared genetic basis with hair colour and lifespan

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Combined burden and functional impact tests for cancer driver discovery using DriverPower

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Genomic footprints of activated telomere maintenance mechanisms in cancer

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Genetic variation at PPP1R3B increases hepatic CT attenuation and interacts with prandial status on plasma glucose

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Impact of glucose on risk of dementia: Mendelian randomisation studies in 115,875 individuals

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Repositioning of the global epicentre of non-optimal cholesterol

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Impact of Glucose Level on Micro- and Macrovascular Disease in the General Population: A Mendelian Randomization Study

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  • Viktoria Gusarova
  • Colm O'Dushlaine
  • Tanya M. Teslovich
  • Peter N. Benotti
  • Tooraj Mirshahi
  • Omri Gottesman
  • Cristopher V. Van Hout
  • Michael F. Murray
  • Anubha Mahajan
  • Jonas B. Nielsen
  • Lars Fritsche
  • Anders Berg Wulff
  • Daniel F. Gudbjartsson
  • Marketa Sjögren
  • Connor A. Emdin
  • Robert A. Scott
  • Wen Jane Lee
  • Aeron Small
  • Lydia C. Kwee
  • Om Prakash Dwivedi
  • Rashmi B. Prasad
  • Shannon Bruse
  • Alexander E. Lopez
  • John Penn
  • Anthony Marcketta
  • Joseph B. Leader
  • Christopher D. Still
  • H. Lester Kirchner
  • Uyenlinh L. Mirshahi
  • Amr H. Wardeh
  • Cassandra M. Hartle
  • Lukas Habegger
  • Samantha N. Fetterolf
  • Teresa Tusie-Luna
  • Andrew P. Morris
  • Hilma Holm
  • Valgerdur Steinthorsdottir
  • Patrick Sulem
  • Unnur Thorsteinsdottir
  • Jerome I. Rotter
  • Lee Ming Chuang
  • Scott Damrauer
  • David Birtwell
  • Chad M. Brummett
  • Amit V. Khera
  • Pradeep Natarajan
  • Marju Orho-Melander
  • Jason Flannick
  • Luca A. Lotta
  • Cristen J. Willer
  • Oddgeir L. Holmen
  • Marylyn D. Ritchie
  • David H. Ledbetter
  • Andrew J. Murphy
  • Ingrid B. Borecki
  • Jeffrey G. Reid
  • John D. Overton
  • Ola Hansson
  • Leif Groop
  • Svati H. Shah
  • William E. Kraus
  • Daniel J. Rader
  • Yii Der I. Chen
  • Kristian Hveem
  • Nicholas J. Wareham
  • Sekar Kathiresan
  • Olle Melander
  • Kari Stefansson
  • Børge G. Nordestgaard
  • Anne Tybjærg-Hansen
  • Goncalo R. Abecasis
  • David Altshuler
  • Jose C. Florez
  • Michael Boehnke
  • Mark I. McCarthy
  • George D. Yancopoulos
  • David J. Carey
  • Alan R. Shuldiner
  • Aris Baras
  • Frederick E. Dewey
  • Jesper Gromada
Vis graf over relationer

Angiopoietin-like 4 (ANGPTL4) is an endogenous inhibitor of lipoprotein lipase that modulates lipid levels, coronary atherosclerosis risk, and nutrient partitioning. We hypothesize that loss of ANGPTL4 function might improve glucose homeostasis and decrease risk of type 2 diabetes (T2D). We investigate protein-altering variants in ANGPTL4 among 58,124 participants in the DiscovEHR human genetics study, with follow-up studies in 82,766 T2D cases and 498,761 controls. Carriers of p.E40K, a variant that abolishes ANGPTL4 ability to inhibit lipoprotein lipase, have lower odds of T2D (odds ratio 0.89, 95% confidence interval 0.85-0.92, p = 6.3 × 10-10), lower fasting glucose, and greater insulin sensitivity. Predicted loss-of-function variants are associated with lower odds of T2D among 32,015 cases and 84,006 controls (odds ratio 0.71, 95% confidence interval 0.49-0.99, p = 0.041). Functional studies in Angptl4-deficient mice confirm improved insulin sensitivity and glucose homeostasis. In conclusion, genetic inactivation of ANGPTL4 is associated with improved glucose homeostasis and reduced risk of T2D.

OriginalsprogEngelsk
Artikelnummer2252
TidsskriftNature Communications
Vol/bind9
Udgave nummer1
Sider (fra-til)2252
ISSN2041-1723
DOI
StatusUdgivet - 1 dec. 2018

ID: 55678524