Related Experiment Videos
HDL cholesterol levels in patients with molecularly defined familial hypercholesterolemia
George Miltiadous1, Marios A Cariolou, Moses Elisaf
1Department of Internal Medicine, Medical School, University of Ioannina, Greece.
Insights
Familial hypercholesterolemia (FH) patients
Area of Science:
- Cardiovascular Genetics
- Lipid Metabolism
Background:
- Familial hypercholesterolemia (FH) is a common genetic disorder causing premature atherosclerosis.
- Mutations in the LDL receptor gene lead to high cholesterol levels.
- High-density lipoprotein (HDL) cholesterol is an independent risk factor for coronary heart disease in FH patients.
Purpose of the Study:
- To investigate how LDL receptor gene mutations and specific gene polymorphisms affect HDL cholesterol levels in patients with heterozygous FH.
Main Methods:
- Studied 84 patients with molecularly defined heterozygous FH.
- Analyzed the impact of different LDL receptor gene mutations on HDL cholesterol.
- Assessed common gene polymorphisms (CETP, ApoA-IV, ACE, ApoE) influencing HDL metabolism.
Main Results:
- The specific type of LDL receptor gene mutation did not significantly alter HDL cholesterol levels.
- Apolipoprotein E (ApoE) gene polymorphism significantly affected HDL cholesterol levels.
- Carrying the ApoE E4 allele was linked to lower HDL cholesterol levels in FH patients.
Conclusions:
- HDL cholesterol levels in heterozygous FH patients can be influenced by apolipoprotein E gene polymorphism.
- This finding highlights a potential genetic modifier for cardiovascular risk in FH.
Abstract:
Familial hypercholesterolemia (FH) is the most common genetic disorder leading to premature atherosclerosis. Typically, it is due to mutations in the LDL receptor gene resulting in elevated total and LDL cholesterol levels. The type of the LDL receptor gene mutations may affect the severity of hypercholesterolemia and consequently the incidence of coronary atherosclerosis. Furthermore, high-density lipoprotein (HDL) cholesterol levels have been recently shown to be an independent risk factor for coronary heart disease in this population. We examined the effect of the type of the LDL receptor gene mutations and of common gene polymorphisms possibly affecting HDL metabolism [cholesterol ester transfer protein (CETP), apolipoprotein A-IV (ApoA-IV), angiotensin converting enzyme (ACE), and apolipoprotein E (ApoE)] on HDL cholesterol levels in patients with molecularly defined heterozygous FH who were attending our lipid clinic (n=84). The nature of the LDL receptor gene mutation (81T>G, n=12; 858C>A, n=13; 1285G>A, n=12; 1646G>A, n=22; and 1775G>A, n=25) did not significantly influence HDL cholesterol levels. Unlike other gene polymorphisms, the apolipoprotein (apo) E gene polymorphism did significantly affect these levels. In fact, the presence of the E4 allele was associated with lower HDL cholesterol levels compared to patients not carrying this allele. We conclude that HDL cholesterol levels in heterozygous FH patients may be affected by the apoE gene polymorphism.