The Arg82Cys Polymorphism of the Protein Nepmucin Implies a Role in HDL Metabolism

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  • Sophia Metz, Københavns Universitet
  • ,
  • Nikolaj T Krarup, Københavns Universitet, Department of Cardiology, Aalborg University Hospital
  • ,
  • Thomas Bryrup, Københavns Universitet
  • ,
  • Julie Støy
  • Ehm A Andersson, Københavns Universitet
  • ,
  • Christina Christoffersen, Department of Clinical Biochemistry, Rigshospitalet, Københavns Universitet
  • ,
  • Matt J Neville, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford, UKWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UKOxford NIHR Biomedical Research Centre, Oxford, UK.
  • ,
  • Malene R Christiansen, Københavns Universitet
  • ,
  • Anna E Jonsson, Københavns Universitet
  • ,
  • Daniel R Witte
  • Ulla Kampmann
  • Lars B Nielsen, Department of Clinical Biochemistry, Rigshospitalet
  • ,
  • Niklas R Jørgensen, Department of Clinical Biochemistry, Rigshospitalet, Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
  • ,
  • Fredrik Karpe, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford, UKWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UKOxford NIHR Biomedical Research Centre, Oxford, UK.
  • ,
  • Niels Grarup, Københavns Universitet
  • ,
  • Oluf Pedersen, Københavns Universitet
  • ,
  • Tuomas O Kilpeläinen, Københavns Universitet
  • ,
  • Torben Hansen, Københavns Universitet, Syddansk Universitet

Context: Blood lipid levels are linked to the risk of cardiovascular disease and regulated by genetic factors. A low-frequency polymorphism Arg82Cys (rs72836561) in the membrane protein nepmucin, encoded by CD300LG, is associated with lower fasting concentration of high-density lipoprotein cholesterol (HDLc) and higher fasting triglycerides. However, whether the variant is linked to postprandial lipids and glycemic status remains elusive.

Objective: Here, we augment the genetic effect of Arg82Cys on fasting plasma concentrations of HDL subclasses, postprandial lipemia after a standardized high-fat meal, and glycemic status to further untangle its role in HDL metabolism.

Methods: We elucidated fasting associations with HDL subclasses in a population-based cohort study (Oxford BioBank, OBB), including 4522 healthy men and women. We investigated fasting and postprandial consequences on HDL metabolism in recall-by-genotype (RbG) studies (fasting: 20 carrier/20 noncarrier; postprandial: 7 carrier/17 noncarrier), and shed light on the synergistic interaction with glycemic status.

Results: A lower fasting plasma concentration of cholesterol in large HDL particles was found in healthy male carriers of the Cys82 polymorphism compared to noncarriers, both in the OBB (P = .004) and RbG studies (P = .005). In addition, the Cys82 polymorphism was associated with low fasting plasma concentrations of ApoA1 (P = .008) in the OBB cohort. On the contrary, we did not find differences in postprandial lipemia or 2-hour plasma glucose levels.

Conclusion: Taken together, our results indicate an association between the Arg82Cys variant and a lower concentration of HDL particles and HDLc, especially in larger HDL subclasses, suggesting a link between nepmucin and HDLc metabolism or maturation.

OriginalsprogEngelsk
Artikelnummerbvac034
TidsskriftJournal of the Endocrine Society
Vol/bind6
Nummer5
Sider (fra-til)1-10
Antal sider10
ISSN2472-1972
DOI
StatusUdgivet - 1 maj 2022

Bibliografisk note

© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.

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