Impact of variants within seven candidate genes on statin treatment efficacy
Language English Country Czech Republic Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
23098650
DOI
10.33549/physiolres.932341
PII: 932341
Knihovny.cz E-resources
- MeSH
- Alleles MeSH
- Anticholesteremic Agents therapeutic use MeSH
- Apolipoproteins E genetics MeSH
- Atorvastatin MeSH
- Dyslipidemias blood drug therapy genetics MeSH
- Genetic Variation * MeSH
- Genome, Human MeSH
- Genotype MeSH
- Cholesterol, HDL blood MeSH
- Hypercholesterolemia drug therapy genetics MeSH
- Polymorphism, Single Nucleotide MeSH
- Heptanoic Acids therapeutic use MeSH
- Cholesterol, LDL blood MeSH
- Middle Aged MeSH
- Humans MeSH
- Pyrroles therapeutic use MeSH
- Aged MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Anticholesteremic Agents MeSH
- Apolipoproteins E MeSH
- Atorvastatin MeSH
- Cholesterol, HDL MeSH
- Heptanoic Acids MeSH
- Cholesterol, LDL MeSH
- Pyrroles 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.
References provided by Crossref.org
Cholesterol associated genetic risk score and acute coronary syndrome in Czech males
