Polygenic hypercholesterolemia: examples of GWAS results and their replication in the Czech-Slavonic population
Jazyk angličtina Země Česko Médium print
Typ dokumentu časopisecké články
PubMed
28379035
DOI
10.33549/physiolres.933580
PII: 933580
Knihovny.cz E-zdroje
- MeSH
- celogenomová asociační studie metody MeSH
- dospělí MeSH
- hypercholesterolemie krev epidemiologie genetika MeSH
- jednonukleotidový polymorfismus genetika MeSH
- LDL-cholesterol krev genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- multifaktoriální dědičnost genetika MeSH
- surveillance populace * metody MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika epidemiologie MeSH
- Slovenská republika epidemiologie MeSH
- Názvy látek
- LDL-cholesterol MeSH
Since 2007, the year of their first widespread use, genome-wide association studies (GWAS) have become the "gold standard" for the detection of causal genes and polymorphisms in all fields of human medicine. Cardiovascular disease (CVD), one of the major causes of morbidity and mortality, is no exception. The first GWAS focused on hypercholesterolemia and dyslipidemia as the major CVD determinants. GWAS confirm the importance of most of the previously identified genes (e.g. APOE, APOB, LDL-R) and recognize the importance of new genetic determinants (e.g. within the CILP2 or SORT1 gene clusters). Nevertheless, the results of GWAS still require confirmation by independent studies, as interethnic and interpopulation variability of SNP effects have been reported. We analyzed an association between eight variants within seven through GWAs detected loci and plasma lipid values in the Czech post-MONICA population sample (N=2,559). We confirmed an association (all P<0.01) between plasma LDL-cholesterol values and variants within the CILP2 (rs16996148), SORT1 (rs646776), APOB (rs693), APOE (rs4420638) and LDL-R (rs6511720) genes in both males (N=1,194) and females (N=1,368). In contrast, variants within the APOB (rs515135), PCSK9 (rs11206510) and HMGCoAR (rs12654264) genes did not significantly affect plasma lipid values in Czech males or females. Unweighted gene score values were linearly associated with LDL-cholesterol values both in males (P<0.0005) and females (P<0.00005). We confirmed the effects of some, but not all analyzed SNPs on LDL-cholesterol levels, reinforcing the necessity for replication studies of GWA-detected gene variants.
Citace poskytuje Crossref.org
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