Effect of Loss-of-Function Genetic Variants in PCSK9 on Glycemic Traits, Neurocognitive Impairment, and Hepatobiliary Function

Diabetes Care. 2022 Jan 1;45(1):251-254. doi: 10.2337/dc21-0955.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apolipoproteins B*
  • Heterozygote
  • Humans
  • Phenotype
  • Proprotein Convertase 9* / genetics

Substances

  • Apolipoproteins B
  • PCSK9 protein, human
  • Proprotein Convertase 9

Associated data

  • figshare/10.2337/figshare.16846309