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

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 ± 38.3 102 × μmol/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. 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 ± 38.3 102 × μmol/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. 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 (1Ostlund R.E. McGill J.B. Zeng C.M. Covey D.F. Stearns J. Stenson W.F. Spilburg C.A. Gastrointestinal absorption and plasma kinetics of soy Delta(5)-phytosterols and phytostanols in humans.Am. J. Physiol. Endocrinol. Metab. 2002; 282: E911-E916Crossref PubMed Scopus (220) Google Scholar). In contrast, cholesterol absorption varies between 30% and 80% (2Bosner M.S. Lange L.G. Stenson W.F. Ostlund Jr, R.E. Percent cholesterol absorption in normal women and men quantified with dual stable isotopic tracers and negative ion mass spectrometry.J. Lipid Res. 1999; 40: 302-308Abstract Full Text Full Text PDF PubMed Google Scholar). Two recently discovered ATP binding cassette (ABC) transporters, ABCG5 and ABCG8, play an important role in the regulation of intestinal plant sterol absorption by excreting plant sterols that have already been taken up from the enterocyte back into the intestinal lumen (3Yu L. Hammer R.E. Li-Hawkins J. Bergmann K. von Lutjohann D. Cohen J.C. Hobbs H.H. Disruption of ABCG5 and ABCG8 in mice reveals their crucial role in biliary cholesterol secretion.Proc. Natl. Acad. Sci. USA. 2002; 99: 16237-16242Crossref PubMed Scopus (595) Google Scholar). ABCG5 and ABCG8 are half-transporters that function together as a heterodimer. Formation of a heterodimer is an absolute necessity to direct the ABCG5/G8 heterodimer from the endoplasmic reticulum to the apical membrane (4Graf G.A. Li W.P. Gerard R.D. Gelissen I. White A. Cohen J.C. Hobbs H.H. Coexpression of ATP-binding cassette proteins ABCG5 and ABCG8 permits their transport to the apical surface.J. Clin. Invest. 2002; 110: 659-669Crossref PubMed Scopus (294) Google Scholar). This feature explains earlier observations that mutations in only one of the half-transporters already causes the rare inheritable autosomal recessive disease sitosterolemia (5Lee M. Lu K. Patel S. Genetic basis of sitosterolemia.Curr. Opin. Lipidol. 2001; 12: 141-149Crossref PubMed Scopus (166) Google Scholar, 6Berge K.E. Tian H. Graf G.A. Yu L. Grishin N.V. Schultz J. Kwiterovich P. Shan B. Barnes R. Hobbs H.H. Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters.Science. 2000; 290: 1771-1775Crossref PubMed Scopus (1328) Google Scholar, 7Lee M.H. Lu K. Hazard S. Yu H. Shulenin S. Hidaka H. Kojima H. Allikmets R. Sakuma N. Pegoraro R. Srivastava A.K. Salen G. Dean M. Patel S.B. Identification of a gene, ABCG5, important in the regulation of dietary cholesterol absorption.Nat. Genet. 2001; 27: 79-83Crossref PubMed Scopus (0) Google Scholar). Sitosterolemic patients are characterized by severely increased serum plant sterol concentrations, normal to moderately increased serum cholesterol concentrations, and a high risk to develop coronary heart disease at a very young age (8Bhattacharyya A.K. Connor W. β-Sitosterolemia and xanthomatosis.J. Clin. Invest. 1974; 53: 1033-1043Crossref PubMed Scopus (452) Google Scholar, 9Björkhem I. Boberg K.M. Inborn errors in bile acid biosynthesis and storage of sterols other than cholesterol.in: Scriver C.R. Beaudet A.L. Sly W.S. Valle D. The Metabolic Basis of Inherited Diseases. McGraw Hill, New York1994: 2073-2100Google Scholar). Although not generally accepted, several studies have suggested that increased concentrations of plant sterols are a risk factor for premature atherosclerosis in sitosterolemic patients (10Miettinen T.A. Strandberg T.E. Gylling H. Noncholesterol sterols and cholesterol lowering by long-term simvastatin treatment in coronary patients: relation to basal serum cholestanol.Arterioscler. Thromb. Vasc. Biol. 2000; 20: 1340-1346Crossref PubMed Scopus (196) Google Scholar, 11Miettinen T.A. Gylling H. Lindbohm N. Miettinen T.E. Radhakrishnan A. Rajaratnam A. Relas H. Serum noncholesterol sterols during inhibition of cholesterol synthesis by statins.J. Lab. Clin. Med. 2003; 141: 131-137Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar, 12Miettinen T.A. Gylling H. Strandberg T. Sarna S. Baseline serum cholestanol as predictor of recurrent coronary events in subgroup of Scandinavian Simvastatin Survival Trial.BMJ. 1998; 316: 1127-1130Crossref PubMed Scopus (214) Google Scholar) and even in nonsitosterolemic subjects (13Sudhop T. Gottwald B.M. Bergmann K. Von Serum plant sterols as a potential risk factor for coronary heart disease.Metabolism. 2002; 51: 1519-1521Abstract Full Text PDF PubMed Scopus (184) Google Scholar, 14Glueck C.J. Speirs J. Tracey T. Streicher P. Illig E. Vandegrift J. Relationships of serum plant sterols (phytosterols) and cholesterol in 595 hypercholesterolemic subjects, and familial aggregation of phytosterols, cholesterol, and premature coronary heart disease in hypercholesterolemic probands and their first degree relatives.Metabolism. 1991; 40: 842-848Abstract Full Text PDF PubMed Scopus (178) Google Scholar). Besides the various rare mutations in ABCG5 or ABCG8 as observed in sitosterolemic patients (15Hubacek J.A. Berge K.E. Cohen J.C. Hobbs H.H. Mutations in ATP-binding cassette binding proteins G5 (ABCG5) and 2001; variations in the sitosterolemic have been polymorphisms in ABCG5 and ABCG8 are related to serum plant sterol concentrations K.E. Bergmann K. Von Lutjohann D. R. Hobbs H.H. Cohen J.C. of plasma noncholesterol sterols and to in ABCG5 and Lipid Res. 2002; Full Text Full Text PDF PubMed Google Scholar). It is not whether these variations are also associated with variations in serum plant sterol concentrations during interventions known to affect plant sterol metabolism. We therefore decided to the between changes in serum plant sterol concentrations with ABCG5 and ABCG8 polymorphisms after consumption of plant stanol esters, which are known to decrease plasma plant sterol concentrations. Despite the association between ABCG5 and ABCG8 and intestinal plant sterol the role of ABCG5 and ABCG8 in cholesterol absorption is (3Yu L. Hammer R.E. Li-Hawkins J. Bergmann K. von Lutjohann D. Cohen J.C. Hobbs H.H. Disruption of ABCG5 and ABCG8 in mice reveals their crucial role in biliary cholesterol secretion.Proc. Natl. Acad. Sci. USA. 2002; 99: 16237-16242Crossref PubMed Scopus (595) Google Scholar, L. Li-Hawkins J. Hammer R.E. Berge K.E. Cohen J.C. Hobbs H.H. of ABCG5 and ABCG8 biliary cholesterol and absorption of dietary Clin. Invest. 2002; 110: PubMed Scopus Google Scholar, L. J. Bergmann K. Von Lutjohann D. Cohen J.C. Hobbs H.H. of cholesterol by the ATP-binding cassette transporters G5 and Biol. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar, T. S. K. A.K. Shan B. M. M. in G5 mice is of the Full Text Full Text PDF PubMed Scopus Google Scholar). a of the study was to for between ABCG5 and ABCG8 polymorphisms with changes in LDL cholesterol after consumption of plant stanol of the study have been J. stanol serum and in 2000; Full Text Full Text PDF PubMed Scopus Google Scholar, J. of diets with two plant stanol plasma and 2001; Full Text PDF PubMed Scopus Google Scholar). In were to during a their and for a acid and the subjects were for and to one of The = to the and and the and the same and to which a = or a = plant stanol was The of the have been in J. plant stanol and membrane acid in hypercholesterolemic J. 1999; Scholar). The was at and and the was at the of plant in the was ± ± and in the was ± were with from were by the and the of from and as as cholesterol and not during the study J. stanol serum and in 2000; Full Text Full Text PDF PubMed Scopus Google the of the of of ± ± ± mass ± ± ± cholesterol ± ± ± ± ± ± are ± in a are ± the of the study was in a which was for J. of variation in and with cholesterol and the to plant stanol J. Clin. Invest. 2002; PubMed Scopus Google Scholar). the of the and and at the of the and was in a serum after an from the and from the Serum was by at for at after and were at for of serum plant sterols, plant and cholesterol concentrations at the of the study J. stanol serum and in 2000; Full Text Full Text PDF PubMed Scopus Google Scholar, J. of diets with two plant stanol plasma and 2001; Full Text PDF PubMed Scopus Google Scholar). decided to only between serum plant sterols, and with polymorphisms in ABCG5/G8 with a of the of subjects in a genotype low for In have to only that showed a cross-sectional association with serum plant sterol or LDL cholesterol concentrations in earlier in the of ABCG8 ABCG8 and ABCG5 of and from ABCG8 and of from ABCG5 was by of as (15Hubacek J.A. Berge K.E. Cohen J.C. Hobbs H.H. Mutations in ATP-binding cassette binding proteins G5 (ABCG5) and 2001; Scholar). In were in of of of The of The and was for at ABCG8 of the of at at and at by at ABCG5 the was in that for at and was were with and the were for at a The were by at a a of the have been (15Hubacek J.A. Berge K.E. Cohen J.C. Hobbs H.H. Mutations in ATP-binding cassette binding proteins G5 (ABCG5) and 2001; Scholar). The were and for ABCG8 and and for ABCG5 of the of subjects, and plant sterol concentrations were not significantly and of the T400K ABCG8 and ABCG5 were the not affect the was to and as the of the cross-sectional differences in between genotype were compared with an the genotype were also compared with to were In of their with mass and age were as potential these were not significantly between the various genotype not and were therefore not into the In a for changes in were for as differences between of the and the in serum and plant sterol and stanol concentrations were not between the two J. stanol serum and in 2000; Full Text Full Text PDF PubMed Scopus Google Scholar, J. of diets with two plant stanol plasma and 2001; Full Text PDF PubMed Scopus Google of the and the plant stanol were = of genotype these were with an were by cross-sectional studies K.E. Bergmann K. Von Lutjohann D. R. Hobbs H.H. Cohen J.C. of plasma noncholesterol sterols and to in ABCG5 and Lipid Res. 2002; Full Text Full Text PDF PubMed Google Scholar) have that with the TT genotype have plasma plant sterol concentrations, not to of with from the as and genotype and plant sterol concentrations as The two are which the of into the were with the Scholar). for the in and of ABCG8 and in of ABCG5 are in genotype were in was for two of of the polymorphisms the of the serum concentrations of LDL cholesterol, cholesterol, and in subjects = were ± ± and ± Serum concentrations of plant sterols, plant and at the of the are in of the in and of ABCG8 and in of (0) are absolute in in a between in and of ABCG8 and in of and the were by subjects in the in a between polymorphisms in ABCG8 and ABCG5 with absolute and serum noncholesterol sterol concentrations ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± concentrations × μmol/mmol ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± are ± and were after a of consumption of and in a are absolute in and the were by subjects in the are ± and were after a of consumption of and between the and serum plant sterol concentrations, absolute and × μmol/mmol were of absolute and in the only serum were serum campesterol and sitosterol concentrations were associated with the ABCG8 T400K genotype was The association with serum concentrations (P = for serum plant stanol and concentrations between the No were between the polymorphisms in the ABCG8 with serum and with the genotype showed significantly serum LDL cholesterol concentrations compared with subjects between polymorphisms in ABCG8 and ABCG5 with serum and ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± are ± and were after a of consumption of and in a are ± and were after a of consumption of and In the subjects the plant stanol serum campesterol and sitosterol concentrations of compared with the changes that plant stanol consumption cholesterol absorption and increased cholesterol which is in with the known a LDL cholesterol concentrations were significantly and concentrations were not Changes in serum campesterol and sitosterol concentrations were significantly associated with the ABCG8 T400K The decrease of ± 102 × μmol/mmol cholesterol for campesterol in TT subjects was significantly from the of ± 102 × μmol/mmol in subjects with the genotype to 102 × μmol/mmol The reduction of −57.1 ± 38.3 102 × μmol/mmol cholesterol for sitosterol in TT subjects was also compared with the reduction of ± 102 × μmol/mmol cholesterol in subjects with the (P for the in to 102 × μmol/mmol to the association between the genotype of the ABCG8 T400K and with changes in serum plant sterol and concentrations suggested an relation for serum campesterol and sitosterol concentrations The reduction of −57.1 ± 38.3 102 μmol/mmol cholesterol for sitosterol in TT subjects was significantly greater compared with the −36.0 ± 18.7 in subjects with the TK genotype (P = to 102 × μmol/mmol and the −16.9 ± 13.0 in subjects with the KK genotype (P = to 102 × μmol/mmol Changes in serum campesterol concentrations showed a comparable association with the ABCG8 T400K No between the ABCG8 and ABCG5 polymorphisms with changes in serum plant stanol and concentrations were between polymorphisms in ABCG8 and ABCG5 with changes in absolute and serum noncholesterol sterol concentrations after consumption of plant stanol concentrations ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± concentrations × μmol/mmol ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± are ± Changes in were as the between at the of the and and the and in a between polymorphisms in ABCG8 and ABCG5 with changes in and concentrations after consumption of plant stanol ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± are ± Changes in were as the between at the of the and and the and in a are ± Changes in were as the between at the of the and and the and are ± Changes in were as the between at the of the and and the and Serum plant sterol concentrations between C.J. Speirs J. Tracey T. Streicher P. Illig E. Vandegrift J. Relationships of serum plant sterols (phytosterols) and cholesterol in 595 hypercholesterolemic subjects, and familial aggregation of phytosterols, cholesterol, and premature coronary heart disease in hypercholesterolemic probands and their first degree relatives.Metabolism. 1991; 40: 842-848Abstract Full Text PDF PubMed Scopus (178) Google Scholar, J.A. Serum is an of cholesterol synthesis in Lipid Res. Full Text PDF PubMed Google Scholar) but are stable for a K.E. Bergmann K. Von Lutjohann D. R. Hobbs H.H. Cohen J.C. of plasma noncholesterol sterols and to in ABCG5 and Lipid Res. 2002; Full Text Full Text PDF PubMed Google Scholar, M. P. of plasma and two for J. 2001; PubMed Scopus Google Scholar). This a of plant sterol and explains than 80% of the in serum plant sterol concentrations between K.E. Bergmann K. Von Lutjohann D. R. Hobbs H.H. Cohen J.C. of plasma noncholesterol sterols and to in ABCG5 and Lipid Res. 2002; Full Text Full Text PDF PubMed Google Scholar). In also that variation in ABCG8 a of study showed that subjects with the plant sterol concentrations TT the reduction in serum plant sterol concentrations during consumption of plant stanol that the of the ABCG5/G8 heterodimer is in subjects with the ABCG8 TT This in transport of plant sterols of the back into the intestinal lumen or from the into and in increased serum plant sterol concentrations. these subjects also showed the decrease in serum plant sterol concentrations after consumption of plant is to It is known that serum plant sterol concentrations are by consumption of plant stanol J.A. and reduction of plasma and concentrations in and J. Clin. 1998; PubMed Scopus Google Scholar, H. Radhakrishnan R. Miettinen T.A. of serum cholesterol in women with and cholesterol by dietary women and dietary PubMed Scopus Google Scholar, T.A. P. Gylling H. H. E. of serum cholesterol with in a hypercholesterolemic J. Med. PubMed Scopus Google plant with sterols for into and for into the plant sterol is not by the of plant sterols into the enterocyte during plant stanol consumption not the ABCG8 ABCG8 the same of plant sterols of the and into the lumen and as plant stanol that the concentrations of plant sterols in subjects with the TT genotype a ABCG8 decrease to a greater degree than in other studies the of the of the T400K plant sterol are which the of or the potential of the that the of the ABCG8 T400K polymorphisms is in a but is not to a a or a (15Hubacek J.A. Berge K.E. Cohen J.C. Hobbs H.H. Mutations in ATP-binding cassette binding proteins G5 (ABCG5) and 2001; Scholar). of the polymorphisms showed with serum or concentrations, that ABCG8 and ABCG5 not the serum This with observations in mice diets 2% In these was that of the ABCG8 and ABCG5 increased the absorption of dietary plant sterols but not of cholesterol (3Yu L. Hammer R.E. Li-Hawkins J. Bergmann K. von Lutjohann D. Cohen J.C. Hobbs H.H. Disruption of ABCG5 and ABCG8 in mice reveals their crucial role in biliary cholesterol secretion.Proc. Natl. Acad. Sci. USA. 2002; 99: 16237-16242Crossref PubMed Scopus (595) Google Scholar, L. J. Bergmann K. Von Lutjohann D. Cohen J.C. Hobbs H.H. of cholesterol by the ATP-binding cassette transporters G5 and Biol. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar, T. S. K. A.K. Shan B. M. M. in G5 mice is of the Full Text Full Text PDF PubMed Scopus Google Scholar). a serum and plant sterol concentrations were increased in (3Yu L. Hammer R.E. Li-Hawkins J. Bergmann K. von Lutjohann D. Cohen J.C. Hobbs H.H. Disruption of ABCG5 and ABCG8 in mice reveals their crucial role in biliary cholesterol secretion.Proc. Natl. Acad. Sci. USA. 2002; 99: 16237-16242Crossref PubMed Scopus (595) Google Scholar, L. J. Bergmann K. Von Lutjohann D. Cohen J.C. Hobbs H.H. of cholesterol by the ATP-binding cassette transporters G5 and Biol. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar) and T. S. K. A.K. Shan B. M. M. in G5 mice is of the Full Text Full Text PDF PubMed Scopus Google Scholar) serum cholesterol concentrations were not concentrations in the were which was attributable to a biliary cholesterol biliary plant sterol was not in that but in of the increased plant sterol is that biliary plant sterol was as In with these Yu L. Li-Hawkins J. Hammer R.E. Berge K.E. Cohen J.C. Hobbs H.H. of ABCG5 and ABCG8 biliary cholesterol and absorption of dietary Clin. Invest. 2002; 110: PubMed Scopus Google Scholar) that of ABCG8 and ABCG5 significantly serum plant sterol concentrations, serum cholesterol concentrations were not between and In to from the studies with the was that these mice showed a reduction in cholesterol by the the cholesterol absorption to the increased of biliary cholesterol to the intestinal lumen from the the whether intestinal cholesterol absorption is also In biliary cholesterol increased to cholesterol The and serum cholesterol concentrations by a to in cholesterol in ABCG5/G8 and mice showed that ABCG5 and ABCG8 affect serum plant sterol concentrations but not of In that ABCG8 and ABCG5 play a role in the intestinal absorption of plant sterols, ABCG8 and ABCG5 are in the of cholesterol into bile and also of plant ATP binding cassette G5 affect cholesterol concentrations in Genet. 2002; PubMed Scopus Google Scholar) that subjects with the ABCG5 genotype serum cholesterol concentrations than with the to dietary were not related to studies not between these polymorphisms with serum concentrations K.E. Bergmann K. Von Lutjohann D. R. Hobbs H.H. Cohen J.C. of plasma noncholesterol sterols and to in ABCG5 and Lipid Res. 2002; Full Text Full Text PDF PubMed Google Scholar, K. ATP binding cassette G5 and and plasma and after treatment with Lipid Res. Full Text Full Text PDF PubMed Scopus Google Scholar, H. M. J. J. M. R. Miettinen T.A. Polymorphisms in the ABCG5 and ABCG8 with cholesterol absorption and Lipid Res. Full Text Full Text PDF PubMed Scopus Google a significantly serum LDL cholesterol in subjects with the genotype compared with of the In a a association was observed between the ABCG8 and the reduction in LDL cholesterol during treatment K. ATP binding cassette G5 and and plasma and after treatment with Lipid Res. Full Text Full Text PDF PubMed Scopus Google Scholar). In Gylling H. M. J. J. M. R. Miettinen T.A. Polymorphisms in the ABCG5 and ABCG8 with cholesterol absorption and Lipid Res. Full Text Full Text PDF PubMed Scopus Google Scholar) recently showed that the of treatment in subjects earlier K. ATP binding cassette G5 and and plasma and after treatment with Lipid Res. Full Text Full Text PDF PubMed Scopus Google Scholar) related to the cholesterol synthesis and cholesterol absorption in these subjects compared with treatment plasma plant sterol concentrations (10Miettinen T.A. Strandberg T.E. Gylling H. Noncholesterol sterols and cholesterol lowering by long-term simvastatin treatment in coronary patients: relation to basal serum cholestanol.Arterioscler. Thromb. Vasc. Biol. 2000; 20: 1340-1346Crossref PubMed Scopus (196) Google Scholar, 11Miettinen T.A. Gylling H. Lindbohm N. Miettinen T.E. Radhakrishnan A. Rajaratnam A. Relas H. Serum noncholesterol sterols during inhibition of cholesterol synthesis by statins.J. Lab. Clin. Med. 2003; 141: 131-137Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar, 12Miettinen T.A. Gylling H. Strandberg T. Sarna S. Baseline serum cholestanol as predictor of recurrent coronary events in subgroup of Scandinavian Simvastatin Survival Trial.BMJ. 1998; 316: 1127-1130Crossref PubMed Scopus (214) Google have been to changes in serum plant sterol concentrations during treatment were also related to in the ABCG8 these studies have not a between ABCG5 or ABCG8 with serum or concentrations. the that the T400K in ABCG8 is associated with changes in plant sterol with stanol but not with changes in the cholesterol that variation in the of plant is not by the of the reduction in intestinal cholesterol absorption that the ABCG8 genotype to serum plant sterol concentrations after In plasma plant sterol concentrations in serum plant sterol concentrations are after treatment with (10Miettinen T.A. Strandberg T.E. Gylling H. Noncholesterol sterols and cholesterol lowering by long-term simvastatin treatment in coronary patients: relation to basal serum cholestanol.Arterioscler. Thromb. Vasc. 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Strandberg T. Sarna S. Baseline serum cholestanol as predictor of recurrent coronary events in subgroup of Scandinavian Simvastatin Survival Trial.BMJ. 1998; 316: 1127-1130Crossref PubMed Scopus (214) Google Scholar). observations not that increased plant sterol concentrations the of to subjects with the ABCG8 TT genotype were in is to whether have for treatment of In serum campesterol and sitosterol concentrations, as as their changes after consumption of plant are related to a variation in the ABCG8 that is in of the No with serum and concentrations was This that changes in the of the ABCG5/G8 heterodimer plasma sterol concentrations, but not of these to in other studies with other these have for a treatment The are to for serum plant sterol concentrations and to M. M. A. for dietary the This study was by the for and by the

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