Apolipoprotein A-V: a potential modulator of plasma triglyceride levels in Turks

J Lipid Res. 2006 Jan;47(1):144-53. doi: 10.1194/jlr.M500343-JLR200. Epub 2005 Oct 28.

Abstract

The apolipoprotein A-V gene (APOA5) plays an important role in determining plasma triglyceride levels. We studied the effects of APOA5 polymorphisms on plasma triglyceride levels in Turks, a population with low levels of HDL cholesterol and a high prevalence of coronary artery disease. We found 15 polymorphisms, three of which were novel. Seven haplotype-tagging single nucleotide polymorphisms (SNPs) were chosen and genotyped in approximately 3,000 subjects. The rare alleles of the -1464T>C, -1131T>C, S19W, and 1259T>C SNPs were significantly associated with increased triglyceride levels (19-86 mg/dl; P < 0.05) and had clear gene-dose effects. Haplotype analysis of the nine common APOA5 haplotypes revealed significant effects on triglyceride levels (P < 0.001). Detailed analysis of haplotypes clearly showed that the -1464T>C polymorphism had no effect by itself but was a marker for the -1131T>C, S19W, and 1259T>C polymorphisms. The -1131T>C and 1259T>C polymorphisms were in a strong but incomplete linkage disequilibrium and appeared to have independent effects. Thus, the APOA5 -1131T>C, S19W, and 1259T>C rare alleles were associated with significant increases in plasma triglyceride levels. At least one of these alleles was present in approximately 40% of the Turks. Similar associations were observed for -1131T>C and S19W in white Americans living in San Francisco, California.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Alleles
  • Apolipoprotein A-V
  • Apolipoproteins / genetics*
  • Apolipoproteins A
  • Arabs / genetics
  • Cholesterol, HDL / blood
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / genetics
  • Cross-Sectional Studies
  • European Continental Ancestry Group / genetics
  • Female
  • Gene Frequency
  • Haplotypes
  • Humans
  • Linkage Disequilibrium
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Triglycerides / blood*
  • Triglycerides / genetics*
  • Turkey
  • United States

Substances

  • APOA5 protein, human
  • Apolipoprotein A-V
  • Apolipoproteins
  • Apolipoproteins A
  • Cholesterol, HDL
  • Triglycerides