A Null Mutation in Human APOC3 Confers a Favorable Plasma Lipid Profile and Apparent Cardioprotection
By T. Pollin, Coleen Damcott, Haiqing Shen, Sandra H. Ott, John Shelton, R. Horenstein, Wendy S. Post, J. Mclenithan, L. Bielak, P. Peyser and 4 more. Science, 2008
705 citations recorded by the source corpus.
Apolipoprotein C-III (apoC-III) inhibits triglyceride hydrolysis and has been implicated in coronary artery disease. Through a genome-wide association study, we have found that about 5% of the Lancaster Amish are heterozygous carriers of a null mutation (R19X) in the gene encoding apoC-III (APOC3) and, as a result, express half the amount of apoC-III present in noncarriers. Mutation carriers compared with noncarriers had lower fasting and postprandial serum triglycerides, higher levels of HDL-cholesterol and lower levels of LDL-cholesterol. Subclinical atherosclerosis, as measured by coronary artery calcification, was less common in carriers than noncarriers, which suggests that lifelong deficiency of apoC-III has a cardioprotective effect.
Subfields: Cardiology and Cardiovascular Medicine, Endocrinology, Diabetes and Metabolism, Surgery
View Paper: https://www.semanticscholar.org/paper/d46146fa9f89ec4722b99bade97f6a1d685409c0
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Endocrinology, Diabetes and Metabolism
In Surgery
Citations in the corpus
- Candidate Causal Regulatory Effects by Integration of Expression QTLs with Complex Trait Genetic Associations (2010, background): “The biological interpretation of genome-wide association study (GWAS) signals [1–5] is very challenging since most candidate loci fall either in gene deserts or in regions with many equally plausible causative genes.”
- Human knockouts and phenotypic analysis in a cohort with a high rate of consanguinity (2017, positive): “These data show that complete lack of apoC3 markedly improves clearance of plasma triglycerides after a fatty meal and are consistent with and extend an earlier report of diminished post-prandial lipaemia in APOC3 pLoF heterozygotes 25 .”
- Distribution and Medical Impact of Loss-of-Function Variants in the Finnish Founder Population (2014, background): “5–5%) variants in complex diseases and traits such as triglycerides [1], insulin processing [2], bone mineral density [3], Alzheimer’s disease [4], impulsivity [5], and prostate cancer [6], some of which confer protection from disease [4].”
- Applications of genome editing technology in the targeted therapy of human diseases: mechanisms, advances and prospects (2020, background): “The blood level of triglyceride (TG) in subjects with nonsense mutations in the apolipoprotein C3 (APOC3) gene was significantly lower than that in unaffected people (an allelic mutation corresponds to a 40% decrease).(96) The incidence of heart disease in both carriers was lower than that in unaffe”