Document Detail

Population-based resequencing of ANGPTL4 uncovers variations that reduce triglycerides and increase HDL.
MedLine Citation:
PMID:  17322881     Owner:  NLM     Status:  MEDLINE    
Resequencing genes provides the opportunity to assess the full spectrum of variants that influence complex traits. Here we report the first application of resequencing to a large population (n = 3,551) to examine the role of the adipokine ANGPTL4 in lipid metabolism. Nonsynonymous variants in ANGPTL4 were more prevalent in individuals with triglyceride levels in the lowest quartile than in individuals with levels in the highest quartile (P = 0.016). One variant (E40K), present in approximately 3% of European Americans, was associated with significantly lower plasma levels of triglyceride and higher levels of high-density lipoprotein cholesterol in European Americans from the Atherosclerosis Risk in Communities Study and in Danes from the Copenhagen City Heart Study. The ratio of nonsynonymous to synonymous variants was higher in European Americans than in African Americans (4:1 versus 1.3:1), suggesting population-specific relaxation of purifying selection. Thus, resequencing of ANGPTL4 in a multiethnic population allowed analysis of the phenotypic effects of both rare and common variants while taking advantage of genetic variation arising from ethnic differences in population history.
Stefano Romeo; Len A Pennacchio; Yunxin Fu; Eric Boerwinkle; Anne Tybjaerg-Hansen; Helen H Hobbs; Jonathan C Cohen
Publication Detail:
Type:  Journal Article; Multicenter Study; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2007-02-25
Journal Detail:
Title:  Nature genetics     Volume:  39     ISSN:  1061-4036     ISO Abbreviation:  Nat. Genet.     Publication Date:  2007 Apr 
Date Detail:
Created Date:  2007-03-29     Completed Date:  2007-06-06     Revised Date:  2013-06-06    
Medline Journal Info:
Nlm Unique ID:  9216904     Medline TA:  Nat Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  513-6     Citation Subset:  IM    
Donald W. Reynolds Cardiovascular Clinical Research Center, the Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA.
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MeSH Terms
African Americans / genetics
Cholesterol, HDL / blood*
Cohort Studies
Energy Metabolism / genetics
European Continental Ancestry Group / genetics
Gene Frequency
Genetic Linkage*
Hispanic Americans / genetics
Intercellular Signaling Peptides and Proteins / genetics*,  physiology
Middle Aged
Polymorphism, Single Nucleotide* / physiology
Sequence Analysis, DNA*
Triglycerides / blood*
Grant Support
Reg. No./Substance:
0/ANGPTL4 protein, human; 0/Angiopoietins; 0/Cholesterol, HDL; 0/Intercellular Signaling Peptides and Proteins; 0/Triglycerides
Comment In:
Nat Genet. 2007 Apr;39(4):439-40   [PMID:  17392801 ]

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