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An LDLR missense variant poses high risk of familial hypercholesterolemia in 30% of Greenlanders and offers potential of early cardiovascular disease intervention.
Jørsboe, Emil; Andersen, Mette K; Skotte, Line; Stæger, Frederik F; Færgeman, Nils J; Hanghøj, Kristian; Santander, Cindy G; Senftleber, Ninna K; Diaz, Lars J; Overvad, Maria; Waples, Ryan K; Geller, Frank; Bjerregaard, Peter; Melbye, Mads; Larsen, Christina V L; Feenstra, Bjarke; Jørgensen, Marit E; Grarup, Niels; Moltke, Ida; Albrechtsen, Anders; Hansen, Torben.
Afiliación
  • Jørsboe E; Bioinformatics Centre, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
  • Andersen MK; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Skotte L; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Stæger FF; Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
  • Færgeman NJ; Bioinformatics Centre, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
  • Hanghøj K; Villum Center for Bioanalytical Sciences, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Denmark.
  • Santander CG; Bioinformatics Centre, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
  • Senftleber NK; Bioinformatics Centre, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
  • Diaz LJ; Bioinformatics Centre, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
  • Overvad M; Steno Diabetes Center Copenhagen, Gentofte, Denmark.
  • Waples RK; Steno Diabetes Center Copenhagen, Gentofte, Denmark.
  • Geller F; Steno Diabetes Center Copenhagen, Gentofte, Denmark.
  • Bjerregaard P; Bioinformatics Centre, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
  • Melbye M; Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
  • Larsen CVL; National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark.
  • Feenstra B; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
  • Anders Koch; Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
  • Jørgensen ME; K.G.Jebsen Center for Genetic Epidemiology, Norwegian University of Science and Technology (NTNU), Norway.
  • Grarup N; Center for Fertility and Health, Norwegian Institute of Public Health, Norway.
  • Moltke I; National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark.
  • Albrechtsen A; Greenland Centre for Health Research, University of Greenland, Nuuk, Greenland.
  • Hansen T; Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
HGG Adv ; 3(4): 100118, 2022 Oct 13.
Article en En | MEDLINE | ID: mdl-36267056
The common Arctic-specific LDLR p.G137S variant was recently shown to be associated with elevated lipid levels. Motivated by this, we aimed to investigate the effect of p.G137S on metabolic health and cardiovascular disease risk among Greenlanders to quantify its impact on the population. In a population-based Greenlandic cohort (n = 5,063), we tested for associations between the p.G137S variant and metabolic health traits as well as cardiovascular disease risk based on registry data. In addition, we explored the variant's impact on plasma NMR measured lipoprotein concentration and composition in another Greenlandic cohort (n = 1,629); 29.5% of the individuals in the cohort carried at least one copy of the p.G137S risk allele. Furthermore, 25.4% of the heterozygous and 54.7% of the homozygous carriers had high levels (>4.9 mmol/L) of serum LDL cholesterol, which is above the diagnostic level for familial hypercholesterolemia (FH). Moreover, p.G137S was associated with an overall atherosclerotic lipid profile, and increased risk of ischemic heart disease (HR [95% CI], 1.51 [1.18-1.92], p = 0.00096), peripheral artery disease (1.69 [1.01-2.82], p = 0.046), and coronary operations (1.78 [1.21-2.62], p = 0.0035). Due to its high frequency and large effect sizes, p.G137S has a marked population-level impact, increasing the risk of FH and cardiovascular disease for up to 30% of the Greenlandic population. Thus, p.G137S is a potential marker for early intervention in Arctic populations.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Etiology_studies / Risk_factors_studies Idioma: En Revista: HGG Adv Año: 2022 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Etiology_studies / Risk_factors_studies Idioma: En Revista: HGG Adv Año: 2022 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Estados Unidos