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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1995;15:1009-1014.)
© 1995 American Heart Association, Inc.

Articles

Determinants of Lipid Levels Among Children With Heterozygous Familial Hypercholesterolemia in Norway

Serena Tonstad; Trond P. Leren; Mette Sivertsen; Leiv Ose

From the Lipid Clinic, Medical Department A, National Hospital (S.T., M.S., L.O.), and the Department of Medical Genetics, Ullevål University Hospital (T.P.L.), Oslo, Norway.

Correspondence to S. Tonstad, MD, MPH, Lipid Clinic, Rikshospitalet, N-0027 Oslo, Norway.

Abstract Three founder mutations have been discovered among individuals with familial hypercholesterolemia (FH) in Norway: FH_Elverum and FH_Svartor, predicted to be null alleles, and FH_C210G, predicted to disrupt the secondary structure of the ligand-binding domain. To clarify the effect of these and other mutations on lipid levels and parental history of premature cardiovascular disease, we examined 164 boys and girls ages 6 to 16 years with heterozygous FH. Among all children, serum cholesterol levels of the FH parent, percent body fat, pubertal stage, and serum cholesterol levels of the non-FH parent, but not apo E polymorphism, were significant determinants of LDL cholesterol levels in a stepwise multiple regression equation and explained 40% (95% confidence interval [CI], 25% to 55%) of the variance in LDL cholesterol. Among boys, percent body fat, dietary sucrose, and apo E genotype determined 31% (95% CI, 14% to 49%) of the variance in triglyceride levels; whereas among girls, only percent body fat was associated with triglyceride levels. Percent body fat was not associated with LDL cholesterol or triglyceride levels in the FH_C210G group. The children's and FH parents' lipid levels and premature cardiovascular disease among parents were similar among the null-allele and defective-protein groups and in those with an undetected mutation. These data confirm that the phenotypic expression of FH in childhood is influenced by modifiable lifestyle characteristics and by genetic factors other than the underlying mutation and raise the possibility that body fatness may interact with genotype in determining lipid levels.

Key Words: familial hypercholesterolemia • LDL receptor mutation • apo E • dietary intake, children

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