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The lipoprotein lipase (Asn291 → Ser) mutation is associated with elevated lipid levels in families with familial combined hyperlipidaemia

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Author: Hoffer, M.J.V. · Bredie, S.J.H. · Boomsma, D.I. · Reymer, P.W.A. · Kastelein, J.J.P. · Knijff, P. de · Demacker, P.N.M. · Stalenhoef, A.F.H. · Havekes, L.M. · Frants, R.R.
Type:article
Date:1996
Institution: Gaubius Instituut TNO
Source:Atherosclerosis, 2, 119, 159-167
Identifier: 233197
doi: doi:10.1016/0021-9150(95)05641-6
Keywords: Biology · Cholesterol · Familial combined hyperlipidaemia · Lipoprotein lipase · LPL(Asn291→ Ser) mutation · Triglycerides · cholesterol · high density lipoprotein cholesterol · lipoprotein lipase · low density lipoprotein cholesterol · triacylglycerol · very low density lipoprotein · adult · article · controlled study · coronary artery atherosclerosis · enzyme activity · familial hyperlipemia · gene mutation · genetic predisposition · human · major clinical study · male · pedigree analysis · priority journal · Base Sequence · Cholesterol · Coronary Disease · Female · Gene Frequency · Genetic Predisposition to Disease · Heterozygote · Humans · Hyperlipidemia, Familial Combined · Lipids · Lipoprotein Lipase · Male · Molecular Sequence Data · Netherlands · Pedigree · Point Mutation · Prevalence · Risk Factors · Triglycerides

Abstract

Familial combined hyperlipidaemia (FCHL) is one of the major genetic causes of coronary heart disease (CHD) and is characterised by elevated levels of plasma cholesterol and/or triglycerides in individuals within a single family. Decreased lipoprotein lipase (LPL) activity has been found in some cases of FCHL. A recent study revealed a common mutation in the LPL gene, LPL(Asn291 → Ser), with a frequency of 9.3% in Dutch FCHL patients (Reymer et al., Circulation, 90 (1994) I-998). This mutation was found in 3 out of 17 FCHL families. Extensive family studies were subsequently performed to determine the effect of this mutation on the phenotypic expression of FCHL. Using a pedigree-based maximum likelihood estimate, we demonstrated that the LPL(Asn291 → Ser) mutation significantly affects the levels of plasma and very low density lipoprotein (VLDL) triglycerides (2.03 ± 0.21 vs. 1.14 ± 0.13 and 1.21 ± 0.16 vs. 0.62 ± 0.09 mmol/l, carriers and non-carriers, respectively) and VLDL- and high density lipoprotein (HDL) cholesterol(0.83 ± 0.10 vs. 0.38 ± 0.06 and 1.02 ± 0.08 vs. 1.29 ± 0.05 mmol/l, carriers and non-carriers, respectively), but not those of plasma and low density lipoprotein (LDL) cholesterol. These findings indicate that the LPL(Asn291 → Ser) mutation is associated with elevated lipid levels, indicating it may be one of the genetic factors predisposing to FCHL in the families studied. Chemicals/CAS: Cholesterol, 57-88-5; Lipids; Lipoprotein Lipase, EC 3.1.1.34; Triglycerides