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.
authors.affiliation: Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA. tpollin@medicine.umaryland.edu
authors.forename: Toni I
authors.initials: TI
authors.lastname: Pollin
authors.forename: Coleen M
authors.initials: CM
authors.lastname: Damcott
authors.forename: Haiqing
authors.initials: H
authors.lastname: Shen
authors.forename: Sandra H
authors.initials: SH
authors.lastname: Ott
authors.forename: John
authors.initials: J
authors.lastname: Shelton
authors.forename: Richard B
authors.initials: RB
authors.lastname: Horenstein
authors.forename: Wendy
authors.initials: W
authors.lastname: Post
authors.forename: John C
authors.initials: JC
authors.lastname: McLenithan
authors.forename: Lawrence F
authors.initials: LF
authors.lastname: Bielak
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Peyser
authors.forename: Braxton D
authors.initials: BD
authors.lastname: Mitchell
authors.forename: Michael
authors.initials: M
authors.lastname: Miller
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: O'Connell
authors.forename: Alan R
authors.initials: AR
authors.lastname: Shuldiner
mesh_terms: D000328:Adult; D053305:Apolipoprotein C-III / Q000097:blood / Q000235:genetics*; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood*; D002835:Christianity; D003324:Coronary Artery Disease / Q000235:genetics / Q000517:prevention & control*; D004041:Dietary Fats / Q000008:administration & dosage; D005215:Fasting; D005260:Female; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D015810:Linkage Disequilibrium; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010414:Pennsylvania; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood*
chemical_list: D053305:Apolipoprotein C-III; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D004041:Dietary Fats; D008055:Lipids; D014280:Triglycerides; D002784:Cholesterol