Polymorphisms in ABCG5 and
ABCG8 Transporters and
Plasma Cholesterol Levels
J. A. HUBÁČEK1,2,3, K.E. BERGE2,4, J.
ŠTEFKOVÁ3, J. PIŤHA1,3, Z. ŠKODOVÁ1,
V. LÁNSKÁ1,
R. POLEDNE1,3
1Institute for Clinical and Experimental Medicine,
Laboratory for Atherosclerosis Research, Prague, Czech Republic,
2Department of Molecular Genetics and McDermott
Centre for Human Growth and Development, University of Texas,
Dallas, USA, 3Center for Experimental Cardiovascular
Research, Prague, Czech Republic and 4Department of
Medical Genetics, Ullevaal University Hospital, Oslo, Norway
Received May 7, 2003
Accepted September 14, 2003
Summary
ABCG5 and ABCG8 transporters play an important role in the
absorption and excretion of sterols. Missence polymorphisms
(Gln604Glu in the ABCG5 and Asp19His, Tyr54Cys, Thr400Lys, and
Ala632Val in the ABCG8) in these genes have been described. In
131 males and 154 females whose dietary composition markedly
changed and lipid parameters decreased over an 8-year follow-up
study (total cholesterol decreased from 6.21±1.31 mmol/l in 1988
to 5.43±1.06 mmol/l in 1996), these polymorphisms were
investigated using PCR. Plasma lipid levels and changes in
plasma lipid levels were independent of the Gln604Glu
polymorphism in ABCG5 and Asp19His and the Ala632Val
polymorphisms in ABCG8. The Tyr54Cys polymorphism influenced the
degree of reduction in total plasma cholesterol (D
–0.49 mmol/l in Tyr54 homozygotes vs.
D
+0.12 mmol/l in Cys54 homozygotes, p<0.04) and LDL-cholesterol (D
–0.57 mmol/l in Tyr54 homozygotes vs.
D
+0.04 mmol/l in Cys54 homozygotes, p<0.03) levels between 1988
and 1996 in females, but not in males. Male Thr400 homozygotes
exhibited a greater decrease in total cholesterol (D
–0.90 mmol/l vs.
D
–0.30 mmol/l, p<0.02) and LDL-cholesterol (D
–0.62 mmol/l vs.
D
–0.19 mmol/l, p<0.04) than Lys400 carriers. No such association
was observed in females. We conclude that Tyr54Cys and Thr400Lys
variations in the ABCG8 gene may play a role in the genetic
determination of plasma cholesterol levels and could possibly
influence the gender-specific response of plasma cholesterol
levels after dietary changes. These polymorphisms are of
potential interest as genetic variants that may influence the
lipid profile.
Key words
Lipids • Polymorphism • Cholesterol • Diet • ABCG5 • ABCG8
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