VIEW AN ABSTRACT

Introduction: Familial hypercholesterolemia (FH) is the most common monogenic disease associated with increased risk of atherosclerotic cardiovascular disease (ACVD). FH is caused by mutations in the LDL-receptor or in the Apolipoprotein B (ApoB); rarely occurs changes in other genes. Carriers of these mutations usually have high cholesterol levels, but the quantification of the relationship between these mutations and cholesterol levels in FH patients with ASKVO and in the general population has not yet been analysed in detail. We investigated the presence of these mutations in the Czech population and in patients with ASKVO and analyzed the relationship of these mutations with cholesterol levels.
Methods: We analyzed the presence of the three most common Czech mutations in the genes for the LDL receptor (Asp266Glu and Gly592Glu) and for apoB (Arg3527Gln/Trp) in 6 012 individuals from the post-MONICA study (age 49.7 ± 11.2 years; 53% women) and in 3 097 patients with acute coronary syndrome (ACS) (age 57.6 ± 8.7 years; 100% men).
Results: A total of 38 FH mutation carriers were detected. The prevalence of LDL-R mutations did not differ between patients with ACS and controls (3.0‰ vs. 2.5‰). APOB mutations were significantly more frequent in patients than in the population (3.5‰ vs. 0.5‰; P < 0.0005; OR (95%CI) = 7.1 (2.0-25.5)). Only 1/3 of carriers of the screened mutations had significantly elevated total cholesterol (values in the upper decile of the population distribution - above 7.5 mmol/L).
Conclusion: We described the prevalence of carriers of the most common mutations in LDL receptor and APOB in the Czech population and in Czech patients with ACS. It is not unconditionally true that the presence of the mutation is associated with above-average total or LDL cholesterol values.