Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9

By J. Cohen, A. Pertsemlidis, I. Kotowski, R. Graham, C. Garcia, Helen H. Hobbs. Nature Genetics, 2005

1,394 citations recorded by the source corpus.

View Paper: https://www.semanticscholar.org/paper/15b4350a7128bdf911d9b66a19aca1b82cf8508e

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Citations in the corpus

Medical relevance of protein-truncating variants across 337,205 individuals in the UK Biobank study (2017, methodology): “To minimize the impact of cofounders and unreliable observations, we used a subset of individuals that satisfied all of the following criteria: (1) selfreported white British ancestry, (2) used to compute principal components, (3) not marked as outliers for heterozygosity and missing rates, (4) do n”
Therapeutic RNAi targeting PCSK9 acutely lowers plasma cholesterol in rodents and LDL cholesterol in nonhuman primates (2008, background): “These in vivo studies demonstrate that PCSK9 lowering by siRNA has an acute effect on plasma LDLc, but not HDLc, in NHPs.”
Development and Applications of CRISPR-Cas9 for Genome Engineering (2014, positive): “For example, NHEJ-mediated inactivation of the CCR5 receptor in lymphocytes (Lombardo et al., 2007) may be a viable strategy for circumventing HIV infection, whereas deletion of PCSK9 (Cohen et al., 2005) or angiopoietin (Musunuru et al., 2010) may provide therapeutic effects against statin-resistan”
Molecular biology of PCSK9: its role in LDL metabolism. (2007, background): “Surprisingly, one out of every 50 African-Americans in the population had a nonsense mutation in PCSK9 (either Y142X or C679X; Figure 1) that lowered LDL-C levels by ~40% [27].”
Generalization and Dilution of Association Results from European GWAS in Populations of Non-European Ancestry: The PAGE Study (2013, background): “Although examples have been described of genes carrying both risk and protective mutations [23–25], others clearly exhibit trends toward risk alleles with similar effects (e.”
Testing for an Unusual Distribution of Rare Variants (2011, background): “have a substantial effect on serum low-density lipoprotein cholesterol (LDL-C) [1], these variants influence risk or protection to myocardial infarction by only a factor of 2 [2,3].”