Common sequence variations in ABCG8 are related to plant sterol metabolism in healthy volunteers

Jogchum Plat, Marjolijn C.E. Bragt, and Ronald P. Mensink

Human Biology, Maastricht University, Maastricht

Corresponding Author: J.PLAT{at}HB.UNIMAAS.NL

Background: Polymorphisms in the ATP binding cassette (ABC) transporters ABCG5 and ABCG8 are related to plasma plant sterol concentrations. It is not known however whether these polymorphisms are also associated with variations in serum plant sterol concentrations during interventions known to affect plant sterol metabolism. We therefore decided to relate changes in serum plant sterol concentrations with ABCG5 and ABCG8 polymorphisms after consumption of plant stanol esters, which lower plasma plant sterol concentrations. Methods and results: In agreement with other studies, we have found in 112 non-hypercholesterolemic subjects, that cholesterol-standardized serum campesterol and sitosterol concentrations were significantly associated with ABCG8 T400K genotype. This genotype however was also associated with changes in serum plant sterol concentrations after consumption of plant stanols. The reduction of - 57.1±38.3 102 mmol/mmol cholesterol for sitosterol in TT subjects was significantly greater as compared to that of - 36.0±18.7 in subjects with the TK genotype (P=0.021; 95%CI - 39.1 to - 3.1 102 x mmol/mmol cholesterol) and to that of - 16.9±13.0 in subjects with the KK genotype (P=0.047; 95%CI - 85.2 to - 4.8 102 x mmol/mmol cholesterol). Changes in serum campesterol concentrations showed a comparable association pattern with ABCG8 T400K genotype. No associations with serum total or LDL cholesterol concentrations were found. Finally, other ABCG8 (A632V) or ABCG5 (Q604E) polymorphisms did not show an association with plant sterols. Conclusions: Genetic variation in ABCG8 not only explains cross-sectional differences in serum plant sterol concentrations, but also determines a subjects’ responsiveness to changes in serum plant sterols during interventions known to affect plant sterol metabolism. Whether these findings should have consequences for a patients’ optimal cholesterol-lowering drug treatment, warrants further investigation.

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