Abstract:
Statins, the standard treatment for hypercholesterolaemia, have been associated with side effects, including statin intolerance. This study determined the prevalence of SLCO1B1 single nucleotide variations (SNVs) and possible associations between SLCO1B1 SNVs, statin intolerance and creatine kinase (CK) in hypercholesterolemic patients on statin therapy.
One hundred and eighty one healthy controls and 100 hypercholesterolaemic patients receiving either simvastatin or atorvastatin were recruited. A questionnaire was used to assess the risk of statin intolerance. Polymerase Chain Reaction - Restriction Fragment Length Polymorphism (PCR-RFLP) was used to identify the presence of SLCO1B1 SNVs (rs4149056, rs2306283 and rs4363657) and enzyme-linked immunosorbent assay (ELISA) was used to quantify serum creatine kinase (CK) levels.
Of the 100 hypercholesterolaemic patients, 15% presented with high risk, 49% with moderate risk and 36% with low risk to statin intolerance. The prevalence of the rs4149056 variant was 16% for the control group and 20% for the test group, while the rs2306283 variant present in 31.5% of the control group compared to only 10.5% in the test group. The prevalence of rs4363657 variant was similar in each group. A comparison of genotype frequencies based on calculated statin intolerance risk, i.e. low risk versus moderate to high risk, showed no significant association between any of the SNVs and the either low risk or moderate to high risk statin intolerant presentation. CK levels in patients on simvastatin were significantly higher compared to patients on atorvastatin.
The prevalence of the SLCO1B1 SNVs in this population is a novel finding. No
association between the presence of any one of the SNVs and the statin intolerance severity risk score or CK elevation was found.
