Impact of variants within seven candidate genes on statin treatment efficacy
Jazyk angličtina Země Česko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
23098650
DOI
10.33549/physiolres.932341
PII: 932341
Knihovny.cz E-zdroje
- MeSH
- alely MeSH
- anticholesteremika terapeutické užití MeSH
- apolipoproteiny E genetika MeSH
- atorvastatin MeSH
- dyslipidemie krev farmakoterapie genetika MeSH
- genetická variace * MeSH
- genom lidský MeSH
- genotyp MeSH
- HDL-cholesterol krev MeSH
- hypercholesterolemie farmakoterapie genetika MeSH
- jednonukleotidový polymorfismus MeSH
- kyseliny heptylové terapeutické užití MeSH
- LDL-cholesterol krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- pyrroly terapeutické užití MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- anticholesteremika MeSH
- apolipoproteiny E MeSH
- atorvastatin MeSH
- HDL-cholesterol MeSH
- kyseliny heptylové MeSH
- LDL-cholesterol MeSH
- pyrroly MeSH
Statins are the most commonly used drugs in patients with dyslipidemia. Among the patients, a significant inter-individual variability with supposed strong genetic background in statin treatment efficacy has been observed. Genome wide screenings detected variants within the CELSR2/PSRC1/SORT1, CILP2/PBX4, APOB, APOE/C1/C4, HMGCoA reductase, LDL receptor and PCSK9 genes that are among the candidates potentially modifying response to statins. Ten variants (SNPs) within these genes (rs599838, rs646776, rs16996148, rs693, rs515135, rs4420638, rs12654264, rs6511720, rs6235, rs11206510) were analyzed in 895 (46 % men, average age 60.3+/-13.1 years) patients with dyslipidemia treated with equipotent doses of statins (~90 % on simvastatin or atorvastatin, doses 10 or 20 mg) and selected 672 normolipidemic controls (40 % men, average age 46.5 years). Lipid parameters were available prior to the treatment and after 12 weeks of therapy. Statin treatment resulted in a significant decrease of both total cholesterol (7.00+/-1.53-->5.15+/-1.17 mmol/l, P<0.0001) and triglycerides (2.03+/-1.01-->1.65+/-1.23 mmol/l, P<0.0005). Rs599838 variant was not detected in first analyzed 284 patients. After adjustment for multiple testing, there was no significant association between individual SNPs and statin treatment efficacy. Only the rs4420638 (APOE/C1/C4 gene cluster) G allele carriers seem to show more profitable change of HDL cholesterol (P=0.007 without and P=0.06 after adjustment). Results demonstrated that, although associated with plasma TC and LDL cholesterol per se, variants within the CELSR2/PSRC1/SORT1, CILP2/PBX4, APOB, APOE/C1/C4, HMGCoA reductase, LDL receptor and PCSK9 genes do not modify therapeutic response to statins.
Citace poskytuje Crossref.org
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