© 1998 American Heart Association, Inc.
Original Contributions |
Two Major Loci Control Variation in ß-Lipoprotein Cholesterol and Response to Dietary Fat and Cholesterol in Baboons
From the Departments of Genetics (D.L.R., C.M.K., J.E.H., B.D., J.F.V., S.H.S., L.D.A., J.L.V.) and of Physiology and Medicine (K.D.C., K.S.R., H.C.M.), Southwest Foundation for Biomedical Research, San Antonio, Tex.
Correspondence to David L. Rainwater, PhD, Department of Genetics, Southwest Foundation for Biomedical Research, PO Box 760549, San Antonio, TX 78245-0549. E-mail david{at}darwin.sfbr.org
Abstract—We explored the
genetic control of cholesterolemic responses to dietary
cholesterol and fat in 575 pedigreed baboons. We measured
cholesterol in ß-lipoproteins (low density lipoprotein
cholesterol [LDLC]) in blood drawn from baboons while
they were consuming a baseline (low in cholesterol and fat)
diet, a high–saturated fat (lard) diet, and a
high-cholesterol, high–saturated fat diet. In addition to
baseline levels (LDLCBase), we analyzed two
variables for diet response: LDLCRF, which
represents the LDLC response to increasing dietary fat (ie,
high-fat diet minus baseline), and LDLCRC, which
represents the LDLC response to increasing dietary
cholesterol level (ie, high-cholesterol,
high-fat diet minus high-fat diet). Heritabilities
(h2) of the 3 traits were 0.59 for
LDLCBase, 0.14 for LDLCRF, and 0.59 for
LDLCRC. In addition, LDLCBase and
LDLCRC had a significant genetic correlation (ie,
G=0.54), suggesting that 1 or more genes exert
pleiotropic effects on the 2 traits. Segregation analyses
detected a single major locus that accounted for nearly all genetic
variation in LDLCRC and some genetic variation in
LDLCBase and LDLCRF and confirmed the presence
of a different major locus that influences LDLCBase alone.
Preliminary linkage analyses indicated that neither locus was
linked to the LDL receptor gene, a likely candidate locus for LDLC.
Detection of these major loci with large effects on the LDLC response
to dietary cholesterol in a nonhuman primate offers hope of
detecting and ultimately identifying similar loci that determine LDLC
variation in human populations.
Key Words: LDL • diet • genetics • baboons
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