Abstract 13541: Extremely Low Hdl-Cholesterol and Premature Vascular Disease in Patients With Combined ABCA1 and APOA1 Mutations
Background: Low High-Density Lipoprotein-cholesterol (HDL-c) is a risk factor for cardiovascular disease and mortality. Mutations in the genes for ATP-binding cassette sub-family A-1 (ABCA1) and apolipoprotein A-1 (apoA1) are associated with low levels of HDL-c. We present for the first time two siblings with combined ABCA1 and apoA1 mutations and give a description of their family.
Cases A 48 year old male and his 45 year old sister, both without other risk factors for cardiovascular disease, were found to have a mean HDL-c of 0.24 mmol/l (9.28 mg/dl) due to a combined ABCA-1/apoA1 mutation. The male patient had a myocardial infarction at age 48 needing coronary bypass surgery, while both patients had a coronary artery calcium (CAC) score corresponding to a MESA percentile >99 (3663 and 59 respectively). Genetic testing of 9 family members showed 3 ABCA1 mutation carriers, 5 APOA1 mutations carriers and one person with no mutations. Mean HDL-c was 0.86 mmol/l (33.26 mg/dl) in ABCA1 carriers and 1.0 mmol/l (38.67 mg/dl) in APOA1 carriers, with no obvious differences in atherosclerotic burden or cardiovascular disease.
Conclusion: Our findings support the notion that (very) low HDL-c is associated with premature atherosclerosis. When caused by genetic mutations the effect of low HDL-c levels may be even more pronounced due to lifetime exposure. Furthermore, our results hint at the importance of other factors (like gender) in the genotype-phenotype relationship of these mutations, HDL-c levels and atherosclerosis.
- © 2013 by American Heart Association, Inc.