TY - JOUR
T1 - Modulating effect of the A-278C promoter polymorphism in the cholesterol 7alpha-hydroxylase gene on serum lipid levels in normolipidaemic and hypertriglyceridaemic individuals
AU - Hofman, M.K.
AU - Groenendijk, M.
AU - Verkuijlen, P.J.J.H.
AU - Jonkers, I.J.A.M.
AU - Mohrschladt, M.F.
AU - Smelt, A.H.M.
AU - Princen, H.M.G.
N1 - 000224558500009
PY - 2004
Y1 - 2004
N2 - 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.
AB - 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.
KW - apolipoprotein-e polymorphism
KW - bile-acid kinetics
KW - density-lipoprotein
KW - 7-alpha-hydroxylase gene
KW - cyp7 gene
KW - disease
KW - mice
KW - hyperlipoproteinemia
KW - quantitation
KW - association
U2 - 10.1038/sj.ejhg.5201236
DO - 10.1038/sj.ejhg.5201236
M3 - Article
VL - 12
SP - 935
EP - 941
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
SN - 1018-4813
IS - 11
ER -