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Journal of Lipid Research, Vol. 45, 653-656, April 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

ATP binding cassette transporter G5 and G8 genotypes and plasma lipoprotein levels before and after treatment with atorvastatin

Kouji Kajinami^1,*,,, Margaret E. Brousseau^*,, Chorthip Nartsupha^*,, Jose M. Ordovas^*, and Ernst J. Schaefer^1,*,

^* Lipid Research Laboratory, Division of Endocrinology Metabolism and Molecular Biology, Tufts-New England Medical Center, Boston, MA
Lipid Metabolism Laboratory, Jean Mayer USDA-Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111
Department of Cardiology, Kanazawa Medical University, Daigaku 1-1, Uchinada 920-0293, Japan

¹ To whom correspondence should be addressed. e-mail: Ernst.Schaefer{at}tufts.edu (E.J.S.); kajinami{at}kanazawa-med.ac.jp (K.K.)

The mechanisms responsible for interindividual variation in response to statin therapy remain uncertain. It has been shown that hepatic cholesterol synthesis is associated with ATP binding cassette transporter G5 and G8 (ABCG5/8) activities. To test the hypothesis that genetic variation in ABCG5/8 might influence the plasma lipid response to statin therapy, we examined five nonsynonymous polymorphisms at the ABCG5/8 loci (Q604E, D19H, Y54C, T400K, and A632V) in 338 hypercholesterolemic patients treated with 10 mg atorvastatin. In carriers of the D19H variant, means of posttreatment values and adjusted percent reductions in LDL cholesterol (LDLC) were significantly lower (P = 0.028) and greater (P = 0.036) (112 mg/dl, 39.7%) than those of noncarriers (119 mg/dl, 36.2%), respectively, while no significant difference was observed in percent reductions in total cholesterol. Stepwise multiple regression analysis revealed significant and independent associations with absolute or percent reduction between D19H genotype and posttreatment LDL cholesterol levels. The other polymorphisms were not significantly associated with treatment effects.

These results suggest that, in patients with hypercholesterolemia, the ABCG8 D19H variant is associated with greater LDLC-lowering response to atorvastatin therapy.

Abbreviations: ABCG8, ATP binding cassette transporter G8; apoB, apolipoprotein B; BMI, body mass index; TC, total cholesterol; LDLC, LDL cholesterol; HDLC, HDL cholesterol; TG, triglyceride

Supplementary key words 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor • pharmacogenetics • low density lipoprotein cholesterol • adenosine 5'-triphosphate binding cassette transporter

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