Relationship of genetic variation in genes encoding apolipoprotein A-IV, scavenger receptor BI, HMG-CoA reductase, CETP and apolipoprotein E with cholesterol metabolism and the response to plant stanol ester consumption.
BACKGROUND
Differences in genetic constitution may affect cholesterol metabolism and responses to diet. Identification of common variations in genes related to dietary responsiveness is therefore an attractive goal to be able to prescribe individually tailored diets for the treatment of dyslipidaemia.


METHODS
We have examined relationships between serum lipids and lipoproteins, cholesterol-standardized campesterol and lathosterol concentrations with genetic variation, and the presence of a gene-diet interaction between plant stanol ester consumption. Candidate genes were apolipoprotein A-IV (apoA-IV), scavenger receptor-BI (SR-BI), cholesterol ester transfer protein (CETP), 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, and apolipoprotein E (apoE). These relations were examined in 112 nonhypercholesterolaemic subjects, of whom 70 consumed 3.8-4.0 g plant stanol esters a day for 8 weeks.


RESULTS
At baseline, high-density lipoprotein (HDL) concentrations of 1.56 +/- 0.36 mmol L(-1) in SR-BI-2 allele carriers tended to be lower compared to the 1.72 +/- 0.42 mmol L(-1) in SR-BI-1/1 subjects (P = 0.069). Cholesterol standardized lathosterol concentrations were also lower in the SR-BI-2 allele carriers (P = 0.002). Furthermore, low-density lipoprotein (LDL) cholesterol concentrations in apoE2 subjects, were lower compared to the LDL cholesterol concentration in apoE3 group (P = 0.002) and apoE4 subjects (P < 0.001). No significant differences between the polymorphisms and dietary responsiveness to plant stanol ester consumption could be found, which indicates that it is unlikely that one of the single polymorphisms analysed in this study is a major factor in explaining the variation in serum LDL cholesterol responses.


CONCLUSIONS
These findings suggest that all subjects who want to lower their cholesterol concentration, will benefit from plant stanol ester consumption, irrespective of their apoA-IV, SR-BI, HMG-CoA reductase, CETP, or apoE genotype.
Plat
J
J
Department of Human Biology, Maastricht University, Maastricht, The Netherlands. J.Plat@HB.UNIMAAS.NL
Mensink
R P
RP
D000328:Adult; D001054:Apolipoproteins A / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics*; D018955:CD36 Antigens; D002352:Carrier Proteins / Q000235:genetics*; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism*; D053480:Cholesterol Ester Transfer Proteins; D008078:Cholesterol, LDL / Q000097:blood; D004032:Diet; D005260:Female; D014644:Genetic Variation; D006023:Glycoproteins; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics*; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008565:Membrane Proteins; D010840:Phytosterols; D011110:Polymorphism, Genetic; D011971:Receptors, Immunologic / Q000235:genetics*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D012855:Sitosterols / Q000494:pharmacology*
D001054:Apolipoproteins A; D001057:Apolipoproteins E; D018955:CD36 Antigens; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D008078:Cholesterol, LDL; D006023:Glycoproteins; D008055:Lipids; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D010840:Phytosterols; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D012855:Sitosterols; C022205:apolipoprotein A-IV; C407042:plant stanol ester; C021273:campesterol; C001521:lathosterol; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases