| Title: | Effect of Loss-of-Function Genetic Variants in PCSK9 on Glycemic Traits, Neurocognitive Impairment, and Hepatobiliary Function. |
| Journal: | Diabetes Care |
| Published: | 10 Nov 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/34758978/ |
| DOI: | https://doi.org/10.2337/dc21-0955 |
| URL: | https://diabetesjournals.org/care/article-pdf/45/1/251/636244/dc210955.pdf |
Publication 4752
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Abstract
OBJECTIVE: To evaluate the association between PCSK9 predicted loss-of-function (pLoF) variants and glycemic traits, hepatobiliary function, and neurocognitive traits.</p>
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.</p>
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).</p>
CONCLUSIONS: Our results do not support adverse effects of PCSK9 pLoF variants on glycemic traits, hepatobiliary function, or neurocognitive traits.</p>
5 Keywords
- Apolipoproteins B
- Heterozygote
- Humans
- Phenotype
- Proprotein Convertase 9
4 Authors
- Jonas Ghouse
- Gustav Ahlberg
- Henning Bundgaard
- Morten S Olesen
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