Print Email Facebook Twitter Modulating effect of the A-278C promoter polymorphism in the cholesterol 7alpha-hydroxylase gene on serum lipid levels in normolipidaemic and hypertriglyceridaemic individuals Title Modulating effect of the A-278C promoter polymorphism in the cholesterol 7alpha-hydroxylase gene on serum lipid levels in normolipidaemic and hypertriglyceridaemic individuals 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. Gaubius Instituut TNO Publication year 2004 Abstract 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 18.104.22.168; Triglycerides Subject BiologyBiomedical ResearchCYP7A1HyperlipidaemiaModifier genePolymorphismTriglyceridesapolipoprotein E3cholesterolcholesterol 7alpha monooxygenaseisoproteinlipidlow density lipoproteintriacylglycerolvery low density lipoproteincontrolled studyDNA polymorphismfamilial hypercholesterolemiagene controlhomozygosityhyperlipidemiahyperlipoproteinemia type 3lipid blood levelmajor clinical studypromoter regiontriacylglycerol blood levelAdultAgedCholesterol 7-alpha-HydroxylaseFemaleGene FrequencyGenotypeHumansHypertriglyceridemiaMaleMiddle AgedPolymorphism, GeneticPromoter Regions (Genetics)Triglycerides To reference this document use: http://resolver.tudelft.nl/uuid:57cb537d-4dc4-4184-8dda-78d4a6196d59 DOI https://doi.org/10.1038/sj.ejhg.5201236 TNO identifier 238066 ISSN 1018-4813 Source European Journal of Human Genetics, 12 (11), 935-941 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.