THE LIPOPROTEIN-LIPASE (ASN291-]SER) MUTATION IS ASSOCIATED WITH ELEVATED LIPID-LEVELS IN FAMILIES WITH FAMILIAL COMBINED HYPERLIPIDEMIA

Familial combined hyperlipidaemia (FCHL) is one of the major genetic c auses of coronary heart disease (CHD) and is characterised by elevated levels of plasma cholesterol and/or triglycerides in individuals with in a single family. Decreased lipoprotein lipase (LPL) activity has be en found in some cases of FCHL. A recent study revealed a common mutat ion 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). Thi s mutation was found in 3 out of 17 FCHL families. Extensive family st udies were subsequently performed to determine the effect of this muta tion on the phenotypic expression of FCHL. Using a pedigree-based maxi mum likelihood estimate, we demonstrated that the LPL(Asn291 --> Ser) mutation significantly affects the levels of plasma and very low densi ty lipoprotein (VLDL) triglycerides (2.03 +/- 0.21 vs. 1.14 +/- 0.13 a nd 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 pla sma and low density lipoprotein (LDL) cholesterol. These findings indi cate that the LPL(Asn291 --> Ser) mutation is associated with elevated lipid levels, indicating it may be one of the genetic factors predisp osing to FCHL in the families studied.