The V73M mutation in the hepatic lipase gene is associated with elevated cholesterol levels in four Dutch pedigrees with familial combined hyperlipidemia.
Familial combined hyperlipidemia (FCHL) is a heritable lipid disorder characterized by multiple lipoprotein phenotypes within a single family. Previously, we have shown an increased incidence of mutations in the LPL gene which was associated with elevated levels of very low density lipoprotein (VLDL) and decreased levels of high density lipoprotein among the families studied. Now, we report the results of our study on the hepatic lipase gene. We found the HL V73M variant to be present in four FCHL families. By means of a pedigree-based maximum log-likelihood method we analyzed the effect of this variant on the lipid levels in these families. Carriers of the HL V73M variant revealed significantly higher levels of total cholesterol (P < 0.01) and apoB (P <0.01). These findings show that the HL V73M mutant explains another part of the variability in the phenotype observed among FCHL family members, compared with mutations in the LPL gene. Family analysis shows that in these FCHL families, carriers of mutations in the LPL or HL genes have an increased risk for FCHL compared with their non-carrier relatives.
Hoffer
M J
MJ
MGC-Department of Human Genetics, Leiden University Medical Centre, The Netherlands.
Snieder
H
H
Bredie
S J
SJ
Demacker
P N
PN
Kastelein
J J
JJ
Frants
R R
RR
Stalenhoef
A F
AF
D000328:Adult; D001055:Apolipoproteins B / Q000097:blood; D002784:Cholesterol / Q000097:blood*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006579:Heterozygote; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000097:blood* / Q000235:genetics*; D008049:Lipase / Q000235:genetics*; D008099:Liver / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000502:physiology*; D010375:Pedigree
D001055:Apolipoproteins B; D002784:Cholesterol; D008049:Lipase