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Modulating effect of the A-278C promoter polymorphism in the cholesterol 7alpha-hydroxylase gene on serum lipid levels in normolipidaemic and hypertriglyceridaemic individuals

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Author: Hofman, M.K. · Groenendijk, M. · Verkuijlen, P.J.J.H. · Jonkers, I.J.A.M. · Mohrschladt, M.F. · Smelt, A.H.M. · Princen, H.M.G.
Institution: Gaubius Instituut TNO
Source:European Journal of Human Genetics, 11, 12, 935-941
Identifier: 238066
doi: doi:10.1038/sj.ejhg.5201236
Keywords: Biology · Biomedical Research · CYP7A1 · Hyperlipidaemia · Modifier gene · Polymorphism · Triglycerides · apolipoprotein E3 · cholesterol · cholesterol 7alpha monooxygenase · isoprotein · lipid · low density lipoprotein · triacylglycerol · very low density lipoprotein · controlled study · DNA polymorphism · familial hypercholesterolemia · gene control · homozygosity · hyperlipidemia · hyperlipoproteinemia type 3 · lipid blood level · major clinical study · promoter region · triacylglycerol blood level · Adult · Aged · Cholesterol 7-alpha-Hydroxylase · Female · Gene Frequency · Genotype · Humans · Hypertriglyceridemia · Male · Middle Aged · Polymorphism, Genetic · Promoter Regions (Genetics) · Triglycerides


The rate-limiting enzyme in the conversion of cholesterol into bile acids is cholesterol 7alpha-hydroxylase (CYP7A1). An A to C substitution 278 bp upstream in the promoter of the CYP7A1 gene was found to be associated with variations in serum lipid levels in normolipidaemic populations. In the present study, we investigated the involvement of this polymorphism in four different lipid disorders: hypertriglyceridaemia (HTG), combined hyperlipidaemia (CH), familial dysbetalipoproteinaemia (FD) and familial hypercholesterolaemia (FH). In a normolipidaemic male population, homozygous for the apoE3 isoform, an association was found between the AA genotype and higher levels of serum triglycerides (AA: + 34%, P=0.036). In HTG patients, the AA genotype was associated with significantly higher concentrations of total cholesterol (+ 23%, P=0.005). There was a tendency towards increased levels of serum triglycerides (+ 39%, P=0.06), VLDL-triglycerides (+ 48%, P=0.053) and VLDL-cholesterol (+ 35%, P=0.059). No significant associations were found between serum lipid levels and the CYP7A1 polymorphism in patients with CH, FD and FH. Our results show that the A-278C polymorphism in the CYP7A1 gene has an effect on triglyceride levels in normolipidaemic males and on cholesterol levels in patients with hypertriglyceridaemia. © 2004 Nature Publishing Group All rights reserved. Chemicals / CAS: cholesterol 7alpha monooxygenase, 9037-53-0; cholesterol, 57-88-5; lipid, 66455-18-3; Cholesterol 7-alpha-Hydroxylase, EC; Triglycerides