Epistasis contributes to the genetic buffering of plasma HDL cholesterol in mice

Physiol Genomics. 2010 Nov 29;42A(4):228-34. doi: 10.1152/physiolgenomics.00044.2010. Epub 2010 Sep 21.


Stressful environmental factors, such as a high-fat diet, can induce responses in the expression of genes that act to maintain physiological homeostasis. We observed variation in plasma concentrations of high-density lipoprotein (HDL) cholesterol across inbred mouse strains in response to high dietary fat intake. Several strains, including C57BL/6J, have stable levels of plasma HDL independent of diet, whereas other strains, including DBA2/J, show marked changes in plasma HDL. To explore this phenomenon further, we used publicly available data from a C57BL/6J × DBA/2J intercross to identify genetic factors that associate with HDL under high-fat diet conditions. Our analysis identified an epistatic interaction that plays a role in the buffering of HDL levels in C57BL/6J mice, and we have identified Arl4d as a candidate gene that mediates this effect. Structural modeling further elucidates the interaction of genetic factors that contribute to the robustness of HDL in response to high-fat diet in the C57BL/6J strain.

Publication types

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

MeSH terms

  • ADP-Ribosylation Factors / genetics
  • ADP-Ribosylation Factors / metabolism*
  • Animals
  • Cholesterol, HDL / blood*
  • Crosses, Genetic
  • Dietary Fats / metabolism*
  • Epistasis, Genetic*
  • Female
  • Lipoproteins, HDL / genetics*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Species Specificity


  • Cholesterol, HDL
  • Dietary Fats
  • Lipoproteins, HDL
  • ADP-Ribosylation Factors
  • Arl4D protein, mouse