title: Plasma apoAV levels are markedly elevated in severe hypertriglyceridemia and positively correlated with the APOA5 S19W polymorphism.
abstract: OBJECTIVE
  The recently discovered apoAV is hypothesized to affect triglyceride metabolism by stimulating the lipolysis of triglycerides in VLDL and chylomicrons. We set out to determine the association between increased serum TG levels, plasma apoAV levels, and polymorphism of the APOA5 gene, with specific emphasis on the APOA5 S19W variation. This mutation alters the endoplasmic reticulum signal peptide and is hypothesized to impair apoAV secretion into the circulation.
  
  
  RESULTS
  Two haplotype-tagging APOA5 polymorphisms, APOA5 S19W and APOA5 -1131T>C and plasma apoAV levels were determined in a population of patients with severe hypertriglyceridemia (HTG). As compared to a random control population, the allele frequencies of the APOA5 S19W and -1131T>C rare variants were significantly increased in HTG patients. Furthermore, the HTG population exhibited markedly elevated plasma apoAV levels that were positively correlated with serum TG levels. Plasma apoAV levels were positively correlated with occurrence of the APOA5 S19W rare variant.
  
  
  CONCLUSIONS
  The increased allele frequencies of the APOA5 S19W and -1131T>C rare variants in the HTG population are in agreement with previous reports. Our data show a positive correlation between apoAV and TG levels. Moreover the finding of a positive association between apoAV levels and the APOA5 S19W rare variant is in disagreement with the hypothesis that this variant is poorly secreted.
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Henneman
authors.forename: Frank G
authors.initials: FG
authors.lastname: Schaap
authors.forename: Louis M
authors.initials: LM
authors.lastname: Havekes
authors.forename: Patrick C N
authors.initials: PC
authors.lastname: Rensen
authors.forename: Rune R
authors.initials: RR
authors.lastname: Frants
authors.forename: Arie
authors.initials: A
authors.lastname: van Tol
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hattori
authors.forename: August H M
authors.initials: AH
authors.lastname: Smelt
authors.forename: Ko Willems
authors.initials: KW
authors.lastname: van Dijk
mesh_terms: D000328:Adult; D000483:Alleles; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A / Q000097:blood* / Q000235:genetics*; D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A; D017931:DNA Primers