The lipoprotein lipase (Asn291 → Ser) mutation is associated with elevated lipid levels in families with familial combined hyperlipidaemia
article
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
Chemicals/CAS: Cholesterol, 57-88-5; Lipids; Lipoprotein Lipase, EC 3.1.1.34; Triglycerides
Topics
CholesterolFamilial combined hyperlipidaemiaLipoprotein lipaseLPL(Asn291→ Ser) mutationTriglyceridescholesterolhigh density lipoprotein cholesterollipoprotein lipaselow density lipoprotein cholesteroltriacylglycerolvery low density lipoproteinadultarticlecontrolled studycoronary artery atherosclerosisenzyme activityfamilial hyperlipemiagene mutationgenetic predispositionhumanmajor clinical studymalepedigree analysispriority journalBase SequenceCholesterolCoronary DiseaseFemaleGene FrequencyGenetic Predisposition to DiseaseHeterozygoteHumansHyperlipidemia, Familial CombinedLipidsLipoprotein LipaseMaleMolecular Sequence DataNetherlandsPedigreePoint MutationPrevalenceRisk FactorsTriglycerides
TNO Identifier
233197
ISSN
00219150
Source
Atherosclerosis, 119(2), pp. 159-167.
Pages
159-167
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