A null mutation in human APOC3 confers a favorable plasma lipid profile and apparent cardioprotection

Toni I. Pollin; Coleen M. Damcott; Haiqing Shen; Sandra H. Ott; John Shelton; Richard B. Horenstein; Wendy Post; John C. McLenithan; Lawrence F. Bielak; Patricia A. Peyser; Braxton D. Mitchell; Michael Miller; Jeffrey R. O'Connell; Alan R. Shuldiner

doi:10.1126/science.1161524

A null mutation in human APOC3 confers a favorable plasma lipid profile and apparent cardioprotection

Toni I. Pollin, Coleen M. Damcott, Haiqing Shen, Sandra H. Ott, John Shelton, Richard B. Horenstein, Wendy Post, John C. McLenithan, Lawrence F. Bielak, Patricia A. Peyser, Braxton D. Mitchell, Michael Miller, Jeffrey R. O'Connell, Alan R. Shuldiner

School of Medicine

Research output: Contribution to journal › Article › peer-review

453 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	1702-1705
Number of pages	4
Journal	Science
Volume	322
Issue number	5908
DOIs	https://doi.org/10.1126/science.1161524
State	Published - Dec 12 2008

ASJC Scopus subject areas

General

Access to Document

10.1126/science.1161524

Cite this

Pollin, T. I., Damcott, C. M., Shen, H., Ott, S. H., Shelton, J., Horenstein, R. B., Post, W., McLenithan, J. C., Bielak, L. F., Peyser, P. A., Mitchell, B. D., Miller, M., O'Connell, J. R., & Shuldiner, A. R. (2008). A null mutation in human APOC3 confers a favorable plasma lipid profile and apparent cardioprotection. Science, 322(5908), 1702-1705. https://doi.org/10.1126/science.1161524

@article{833f19536b4a49b7a1289f5ebdf99fac,

title = "A null mutation in human APOC3 confers a favorable plasma lipid profile and apparent cardioprotection",

abstract = "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.",

author = "Pollin, {Toni I.} and Damcott, {Coleen M.} and Haiqing Shen and Ott, {Sandra H.} and John Shelton and Horenstein, {Richard B.} and Wendy Post and McLenithan, {John C.} and Bielak, {Lawrence F.} and Peyser, {Patricia A.} and Mitchell, {Braxton D.} and Michael Miller and O'Connell, {Jeffrey R.} and Shuldiner, {Alan R.}",

year = "2008",

month = dec,

day = "12",

doi = "10.1126/science.1161524",

language = "English (US)",

volume = "322",

pages = "1702--1705",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "5908",

}

TY - JOUR

T1 - A null mutation in human APOC3 confers a favorable plasma lipid profile and apparent cardioprotection

AU - Pollin, Toni I.

AU - Damcott, Coleen M.

AU - Shen, Haiqing

AU - Ott, Sandra H.

AU - Shelton, John

AU - Horenstein, Richard B.

AU - Post, Wendy

AU - McLenithan, John C.

AU - Bielak, Lawrence F.

AU - Peyser, Patricia A.

AU - Mitchell, Braxton D.

AU - Miller, Michael

AU - O'Connell, Jeffrey R.

AU - Shuldiner, Alan R.

PY - 2008/12/12

Y1 - 2008/12/12

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=58149262866&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58149262866&partnerID=8YFLogxK

U2 - 10.1126/science.1161524

DO - 10.1126/science.1161524

M3 - Article

C2 - 19074352

AN - SCOPUS:58149262866

SN - 0036-8075

VL - 322

SP - 1702

EP - 1705

JO - Science

JF - Science

IS - 5908

ER -

A null mutation in human APOC3 confers a favorable plasma lipid profile and apparent cardioprotection

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this