Title
The lipoprotein lipase (Asn291 → Ser) mutation is associated with elevated lipid levels in families with familial combined hyperlipidaemia
Author
Hoffer, M.J.V.
Bredie, S.J.H.
Boomsma, D.I.
Reymer, P.W.A.
Kastelein, J.J.P.
de Knijff, P.
Demacker, P.N.M.
Stalenhoef, A.F.H.
Havekes, L.M.
Frants, R.R.
Gaubius Instituut TNO
Publication year
1996
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
Subject
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
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DOI
https://doi.org/10.1016/0021-9150(95)05641-6
TNO identifier
233197
ISSN
0021-9150
Source
Atherosclerosis, 119 (2), 159-167
Document type
article