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Rigshospitalet - a part of Copenhagen University Hospital
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Effect of Loss-of-Function Genetic Variants in PCSK9 on Glycemic Traits, Neurocognitive Impairment, and Hepatobiliary Function

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DOI

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OBJECTIVE: To evaluate the association between PCSK9 predicted loss-of-function (pLoF) variants and glycemic traits, hepatobiliary function, and neurocognitive traits.

RESEARCH DESIGN AND METHODS: We identified carriers of PCSK9 pLoF variants in UK Biobank exome sequencing data. We assessed the aggregate effects of these variants on lipid and lipoprotein traits, which served as a positive control. Association of PCSK9 pLoF carrier status and glycemic traits, hepatobiliary function, and neurocognitive traits was then evaluated as a measure for adverse effects.

RESULTS: We identified 374 individuals carrying one of 41 unique PCSK9 pLoF variants. As expected, we found that PCSK9 pLoF carriers had significantly lower LDL cholesterol C levels (P = 7.4 × 10-55) and apolipoprotein B levels (P = 7.6 × 10-50) than did noncarriers. However, we found no significant associations between pLoF carrier status and glycemic traits, hepatobiliary function, and neurocognitive traits (P > 0.05).

CONCLUSIONS: Our results do not support adverse effects of PCSK9 pLoF variants on glycemic traits, hepatobiliary function, or neurocognitive traits.

Original languageEnglish
JournalDiabetes Care
Volume45
Issue number1
Pages (from-to)251-254
Number of pages4
ISSN1935-5548
DOIs
Publication statusPublished - 1 Jan 2022

Bibliographical note

© 2021 by the American Diabetes Association.

ID: 75303633