BACKGROUND: Despite a general decline in mean levels across populations, LDL-cholesterol levels remain a major risk factor for acute coronary syndrome (ACS). The APOB, LDL-R, CILP, and SORT-1 genes have been shown to contain variants that have significant effects on plasma cholesterol levels. METHODS AND RESULTS: We examined polymorphisms within these genes in 1191 controls and 929 patients with ACS. Only rs646776 within SORT-1 was significantly associated with a risk of ACS (P < 0.05, AA vs. + G comparison; OR 1.21; 95% CI 1.01-1.45). With regard to genetic risk score (GRS), the presence of at least 7 alleles associated with elevated cholesterol levels was connected with increased risk (P < 0.01) of ACS (OR 1.26; 95% CI 1.06-1.52). Neither total mortality nor CVD mortality in ACS subjects (follow up-9.84 ± 3.82 years) was associated with the SNPs analysed or cholesterol-associated GRS. CONCLUSIONS: We conclude that, based on only a few potent SNPs known to affect plasma cholesterol, GRS has the potential to predict ACS risk, but not ACS associated mortality.

• Keywords
• Acute coronary syndrome, Cholesterol, Polymorphism, Risk estimation,
• MeSH
• Acute Coronary Syndrome * genetics   MeSH
• Cholesterol MeSH
• Genetic Risk Score * MeSH
• Polymorphism, Single Nucleotide genetics   MeSH
• Humans MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic epidemiology   MeSH
• Names of Substances
• Cholesterol MeSH

BACKGROUND: Gene SLCO1B1, encoding solute organic anionic transport polypeptide OATP1B1, belongs to the group of candidates potentially influencing statin treatment safety. OATP1B1 regulates (not only) the hepatic uptake of statins. Its genetic variation was described as an important predictor of statin-associated myopathy in a cohort of patients treated with a maximum dose of simvastatin. However, the impact of SLCO1B1 gene polymorphism on this risk in patients treated with other statins or lower doses of simvastatin needs to be assessed. Therefore, we performed the present study. MATERIAL/METHODS: SLCO1B1 tagging rs4363657 polymorphism was analyzed in 2 groups of patients with dyslipidemia (treated with simvastatin or atorvastatin, 10 or 20 mg per day), subgroup with statin-induced myalgia (N=286), and subgroup (N=707) without myalgia/myopathy, and in 2301 population controls without lipid-lowering treatment. RESULTS: Frequency of the individual genotypes in patients with myalgia/myopathy (TT=62.3%, CT=34.5%, CC=2.8%) did not significantly differ (both P values over 0.19) from that in patients without muscle symptoms (TT=61.4%, CT=32.9%, CC=5.7%) or from the population controls (TT=63.9%, CT=32.5%, CC=3.6%). Null results were also obtained for the dominant and recessive models of the analysis. CONCLUSIONS: In Czech patients treated with low statin doses, there is no association between SLCO1B1 gene polymorphism and risk of myalgia/myopathy.

• MeSH
• Atorvastatin administration & dosage   adverse effects   pharmacokinetics   therapeutic use   MeSH
• Diabetes Mellitus epidemiology   MeSH
• Dyslipidemias drug therapy   genetics   MeSH
• Gene Frequency MeSH
• Genetic Predisposition to Disease MeSH
• Genotype MeSH
• Hepatocytes metabolism   MeSH
• Polymorphism, Single Nucleotide * MeSH
• Smoking epidemiology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Models, Genetic MeSH
• Myalgia chemically induced   epidemiology   genetics   MeSH
• Muscular Diseases chemically induced   epidemiology   genetics   MeSH
• Obesity epidemiology   MeSH
• Liver-Specific Organic Anion Transporter 1 MeSH
• Organic Anion Transporters genetics   physiology   MeSH
• Aged MeSH
• Simvastatin administration & dosage   adverse effects   pharmacokinetics   therapeutic use   MeSH
• Hydroxymethylglutaryl-CoA Reductase Inhibitors administration & dosage   adverse effects   pharmacokinetics   therapeutic use   MeSH
• Dose-Response Relationship, Drug 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
• Geographicals
• Czech Republic epidemiology   MeSH
• Names of Substances
• Atorvastatin MeSH
• Liver-Specific Organic Anion Transporter 1 MeSH
• Organic Anion Transporters MeSH
• Simvastatin MeSH
• SLCO1B1 protein, human MeSH Browser
• Hydroxymethylglutaryl-CoA Reductase Inhibitors MeSH