The molecular basis of familial hypercholesterolemia in the Czech Republic: spectrum of LDLR mutations and genotype-phenotype correlations
Language English Country Ireland Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
22698793
DOI
10.1016/j.atherosclerosis.2012.05.014
PII: S0021-9150(12)00322-X
Knihovny.cz E-resources
- MeSH
- Apolipoproteins B genetics MeSH
- Biomarkers blood MeSH
- Child MeSH
- Adult MeSH
- Phenotype MeSH
- Gene Frequency MeSH
- Genetic Predisposition to Disease MeSH
- Genetic Association Studies MeSH
- Risk Assessment MeSH
- Hyperlipoproteinemia Type II blood diagnosis epidemiology genetics MeSH
- Middle Aged MeSH
- Humans MeSH
- Linear Models MeSH
- Lipids blood MeSH
- Adolescent MeSH
- Young Adult MeSH
- Mutation * MeSH
- DNA Mutational Analysis MeSH
- Receptors, LDL genetics MeSH
- Risk Factors MeSH
- Chi-Square Distribution MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Czech Republic epidemiology MeSH
- Names of Substances
- Apolipoproteins B MeSH
- Biomarkers MeSH
- LDLR protein, human MeSH Browser
- Lipids MeSH
- Receptors, LDL MeSH
BACKGROUND: Familial hypercholesterolemia (FH), a major risk for coronary heart disease, is predominantly associated with mutations in the genes encoding the low-density lipoprotein receptor (LDLR) and its ligand apolipoprotein B (APOB). RESULTS: In this study, we characterize the spectrum of mutations causing FH in 2239 Czech probands suspected to have FH. In this set, we found 265 patients (11.8%) with the APOB mutation p.(Arg3527Gln) and 535 patients (23.9%) with a LDLR mutation. In 535 probands carrying the LDLR mutation, 127 unique allelic variants were detected: 70.1% of these variants were DNA substitutions, 16.5% small DNA rearrangements, and 13.4% large DNA rearrangements. Fifty five variants were novel, not described in other FH populations. For lipid profile analyses, FH probands were divided into groups [patients with the LDLR mutation (LDLR+), with the APOB mutation (APOB+), and without a detected mutation (LDLR-/APOB-)], and each group into subgroups according to gender. The statistical analysis of lipid profiles was performed in 1722 probands adjusted for age in which biochemical data were obtained without FH treatment (480 LDLR+ patients, 222 APOB+ patients, and 1020 LDLR-/APOB- patients). Significant gradients in i) total cholesterol (LDLR+ patients > APOB+ patients = LDLR-/APOB- patients) ii) LDL cholesterol (LDLR+ patients > APOB+ patients = LDLR-/APOB- patients in men and LDLR+patients > APOB+ patients >LDLR-/APOB- patients in women), iii) triglycerides (LDLR-/APOB- patients > LDLR+ patients > APOB+ patients), and iv) HDL cholesterol (APOB+ patients > LDLR-/APOB- patients = LDLR+ patients) were shown. CONCLUSION: Our study presents a large set of Czech patients with FH diagnosis in which DNA diagnostics was performed and which allowed statistical analysis of clinical and biochemical data.
References provided by Crossref.org
LDLR gene rearrangements in Czech FH patients likely arise from one mutational event
Genetics of Familial Hypercholesterolemia: New Insights
Bending of DNA duplexes with mutation motifs
