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Journal of Lipid Research, Vol. 45, 881-888, May 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Influence of sex and diet on quantitative trait loci for HDL cholesterol levels in an SM/J by NZB/BlNJ intercross population

Ron Korstanje^1,*, Renhua Li^*, Timothy Howard, Peter Kelmenson^*, Jan Marshall^*, Beverly Paigen^* and Gary Churchill^*

^* The Jackson Laboratory, 600 Main St., Bar Harbor, ME 04609
Wake Forest University, Winston-Salem, NC

¹ To whom correspondence should be addressed. e-mail: rkorstan{at}jax.org

To investigate the dependence of HDL quantitative trait loci (QTL) on sex and diet, we generated a large intercross population of mice from parental strains SM/J and NZB/BlNJ. We measured HDL levels in progeny fed a chow diet and measured them again after 6, 12, and 16 weeks of feeding a high-fat, high-cholesterol diet. QTL analysis was performed on the 260 female and 253 male F₂ progeny. A total of 13 significant QTL were found. Four QTL were specific to female mice: Hdlq23 (Chr 6, 26 cM), Hdlq26 (Chr 10, 70 cM), Hdlq27 (Chr 15, 48 cM), and Hdlq32 (Chr 19, 40 cM). One significant QTL was specific to male mice: Hdlq29 (Chr 17, 36 cM). In addition, several QTL were found to have effects that were dependent on diet. Sex- and diet-dependent effects were characterized using a linear model-based genome scan method that avoids the potential pitfalls of subdivided data analysis.

The dependence of QTL effects on sex suggests an important role for the sex hormones in HDL regulation. We recommend that sex should be explicitly accounted for in future studies in the genetics of HDL regulation in both mice and humans.

Abbreviations: apoB, apolipoprotein B; ER, estrogen receptors; QTL, quantitative trait locus; LDLR, LDL receptor; LOD, logarithm of the odds; PLTP, phospholipid transfer protein; SR-BI, scavenger receptor class B type I; VLDLR, VLDL receptor

Supplementary key words diet • high density lipoprotein • mice • sex

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