title: The lipoprotein lipase (Asn291-->Ser) mutation is associated with elevated lipid levels in families with familial combined hyperlipidaemia.
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.
authors.affiliation: MGC-Department of Human Genetics, Leiden University, Netherlands.
authors.forename: M J
authors.initials: MJ
authors.lastname: Hoffer
authors.forename: S J
authors.initials: SJ
authors.lastname: Bredie
authors.forename: D I
authors.initials: DI
authors.lastname: Boomsma
authors.forename: P W
authors.initials: PW
authors.lastname: Reymer
authors.forename: J J
authors.initials: JJ
authors.lastname: Kastelein
authors.forename: P
authors.initials: P
authors.lastname: de Knijff
authors.forename: P N
authors.initials: PN
authors.lastname: Demacker
authors.forename: A F
authors.initials: AF
authors.lastname: Stalenhoef
authors.forename: L M
authors.initials: LM
authors.lastname: Havekes
authors.forename: R R
authors.initials: RR
authors.lastname: Frants
mesh_terms: D001483:Base Sequence; D002784:Cholesterol / Q000097:blood; D003327:Coronary Disease / Q000453:epidemiology* / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000097:blood / Q000150:complications / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D008055:Lipids / Q000097:blood*; D008071:Lipoprotein Lipase / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009426:Netherlands / Q000453:epidemiology; D010375:Pedigree; D017354:Point Mutation; D015995:Prevalence; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood
chemical_list: D008055:Lipids; D014280:Triglycerides; D002784:Cholesterol; D008071:Lipoprotein Lipase