Background:
It is well known that familial hypercholesterolemia (FH) is a common inherited disorder that could cause marked elevation of plasma LDL-C level. However, few data exists regarding the clinical impact of plasma levels of VLDL-C and IDL-C as well as the composition of each lipoprotein fraction in FH. Thus, we assessed the hypothesis that the abnormality in LDLR modulates the quality as well as the quantity of lipoprotein other than LDL fraction.
Methods:
We investigated the plasma lipoprotein by ultracentrifugation method about 146 controls (mean age=61.4±17.1yr, mean LDL-C=92.7±61.2mg/dl), 213 heterozygous mutation-determined FH subjects (mean age=46.0±18.0yr, mean LDL-C=225.1±61.2mg/dl), and 16 homozygous mutation-determined FH subjects (mean age=26.9±17.1yr, mean LDL-C=428.6±86.1mg/dl). In addition, we evaluated the composition of each lipoprotein fraction by calculated cholesterol ester (CE) / triglyceride (TG) ratio.
Results:
As shown in the figure, the differences of the levels of TC and LDL-C between these 3 groups as well as those of VLDL-C (19.5±10.4, 25.2±19.3, 29.5±21.4 mg/dl, respectively) and IDL-C (8.3±3.7, 16.8±11.5, 40.0±37.3 mg/dl, respectively) were statistically significant. Moreover, the ratios of CE/TG of each lipoprotein fraction significantly increased in heterozygous FH and homozygous FH group, compared with that of controls, suggesting that the abnormality in LDLR modulate the quality as well as the quantity of each lipoprotein fraction.
Conclusions:
Our results indicate that LDLR participate not only in metabolism of LDL fraction but also in that of VLDL and IDL fractions. Larger amounts of VLDL-C and IDL-C with worse quality should also be additive risk factor in FH subjects.
Lipoprotein metabolism in familial hypercholesterolemia