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Science 12 December 2008:
Vol. 322. no. 5908, pp. 1702 - 1705
DOI: 10.1126/science.1161524
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Reports

A Null Mutation in Human APOC3 Confers a Favorable Plasma Lipid Profile and Apparent Cardioprotection

Toni I. Pollin,1* Coleen M. Damcott,1 Haiqing Shen,1 Sandra H. Ott,1 John Shelton,1 Richard B. Horenstein,1 Wendy Post,2 John C. McLenithan,1,3 Lawrence F. Bielak,4 Patricia A. Peyser,4 Braxton D. Mitchell,1 Michael Miller,1 Jeffrey R. O'Connell,1 Alan R. Shuldiner1,3

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.

1 Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
2 Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
3 Geriatrics Research and Education Clinical Center, Baltimore Veterans Administration Medical Center, Baltimore, MD 21201, USA.
4 Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA.

* To whom correspondence should be addressed. E-mail: tpollin{at}medicine.umaryland.edu

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A. Hiukka, M. Stahlman, C. Pettersson, M. Levin, M. Adiels, S. Teneberg, E. S. Leinonen, L. M. Hulten, O. Wiklund, M. Oresic, et al. (2009)
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APOC3 Mutation, Serum Triglyceride Concentrations, and Coronary Heart Disease.
M. Y. Tsai and J. M. Ordovas (2009)
Clin. Chem. 55, 1274-1276
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