title: Epistasis contributes to the genetic buffering of plasma HDL cholesterol in mice.
abstract: 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.
authors.affiliation: The Jackson Laboratory, Bar Harbor, Maine, USA. lir3@niddk.nih.gov
authors.forename: Renhua H
authors.initials: RH
authors.lastname: Li
authors.forename: Gary A
authors.initials: GA
authors.lastname: Churchill
mesh_terms: D020727:ADP-Ribosylation Factors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D008076:Cholesterol, HDL / Q000097:blood*; D003433:Crosses, Genetic; D004041:Dietary Fats / Q000378:metabolism*; D004843:Epistasis, Genetic; D005260:Female; D008075:Lipoproteins, HDL / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013045:Species Specificity
chemical_list: D008076:Cholesterol, HDL; D004041:Dietary Fats; D008075:Lipoproteins, HDL; D020727:ADP-Ribosylation Factors; C552323:Arl4D protein, mouse