ATP binding cassette protein G5 (ABCG5) and G8 (ABCG8) may be involved in the regulation of intestinal cholesterol absorption. Therefore, genetic variation at these loci may affect blood cholesterol concentrations by influencing dietary responsiveness. We studied the association between the ABCG5 C1950G (Gln640Glu) polymorphism and blood cholesterol concentrations in 486 subjects and responsiveness to dietary cholesterol in 99 participants in dietary trials. Mean baseline cholesterol concentrations were 0.65 +/- 0.22 mmol/l higher in 13 subjects with the G/G genotype than in 473 carriers of the C-allele (95% confidence interval 0.22-1.08 mmol/l). The response of serum total cholesterol to dietary cholesterol tended to be larger in subjects with the G/G genotype as compared with carriers of the C-allele. We suggest that the ABCG5 G/G genotype may increase serum cholesterol concentrations and, possibly responsiveness to dietary cholesterol in humans. Studies in other populations and experimental settings are required to confirm or reject this hypothesis.
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