Abstract
Polymorphisms in the ATP binding cassette (ABC) transporters ABCG5 and ABCG8 are related to plasma plant sterol concentrations. It is not known whether these polymorphisms are also associated with variations in serum plant sterol concentrations during interventions affecting plant sterol metabolism. We therefore decided to study changes in serum plant sterol concentrations with ABCG5/G8 polymorphisms after consumption of plant stanol esters, which decrease plasma plant sterol concentrations. Cholesterol-standardized serum campesterol and sitosterol concentrations were significantly associated with the ABCG8 T400K genotype, as were changes in serum plant sterol concentrations after consumption of plant stanols. The reduction of -57.1 +/- 38.3 10(2) x micromol/mmol cholesterol for sitosterol in TT subjects was significantly greater compared with the -36.0 +/- 18.7 reduction in subjects with the TK genotype (P = 0.021) and the -16.9 +/- 13.0 reduction in subjects with the KK genotype (P = 0.047). Changes in serum campesterol concentrations showed a comparable association. No association with serum LDL cholesterol was found. Genetic variation in ABCG8 not only explains cross-sectional differences in serum plant sterol concentrations but also determines a subject's responsiveness to changes in serum plant sterols during interventions known to affect plant sterol metabolism.
Highlights
Polymorphisms in the ATP binding cassette (ABC) transporters ABCG5 and ABCG8 are related to plasma plant sterol concentrations
Serum plant sterol concentrations vary widely between individuals [14, 25] but are rather stable over time for a given individual [16, 26]. This suggests a strong effect of genetic background on plant sterol metabolism and heritability; it explains more than 80% of the variability in serum plant sterol concentrations between individuals [16]
We found that genetic variation in ABCG8 explained a part of this variability
Summary
Polymorphisms in the ATP binding cassette (ABC) transporters ABCG5 and ABCG8 are related to plasma plant sterol concentrations. It is not known whether these polymorphisms are associated with variations in serum plant sterol concentrations during interventions affecting plant sterol metabolism. Despite the fact that Western diets provide approximately the same amounts of plant sterols and cholesterol, plasma concentrations of cholesterol are much higher This is partly attributable to the very low absorption rates of plant sterols, which are less than 2% for campesterol and less than 1% for sitosterol, the two most abundant plant sterols in nature [1]. Several studies have suggested that increased concentrations of plant sterols are a risk factor for premature atherosclerosis in sitosterolemic patients [10,11,12] and even in nonsitosterolemic subjects [13, 14]
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