Population-based resequencing of ANGPTL4 uncovers variations that reduce triglycerides and increase HDL.

TitlePopulation-based resequencing of ANGPTL4 uncovers variations that reduce triglycerides and increase HDL.
Publication TypeJournal Article
Year of Publication2007
AuthorsRomeo, S, Pennacchio, LA, Fu, Y, Boerwinkle, E, Tybjaerg-Hansen, A, Hobbs, HH, Cohen, JC
JournalNat Genet
Volume39
Issue4
Pagination513-6
Date Published2007 Apr
ISSN1061-4036
KeywordsAdult, African Americans, Angiopoietin-like 4 Protein, Angiopoietins, Cholesterol, HDL, Cohort Studies, Energy Metabolism, European Continental Ancestry Group, Gene Frequency, Genetic Linkage, Hispanic Americans, Humans, Intercellular Signaling Peptides and Proteins, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Sequence Analysis, DNA, Texas, Triglycerides
Abstract

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.

DOI10.1038/ng1984
Alternate JournalNat. Genet.
PubMed ID17322881
PubMed Central IDPMC2762948
Grant ListRL1 HL092550 / HL / NHLBI NIH HHS / United States
RL1 HL092550-02 / HL / NHLBI NIH HHS / United States
U01 HL066681 / HL / NHLBI NIH HHS / United States
HL066681 / HL / NHLBI NIH HHS / United States