Genetic variants weaken the cholesterol-lowering effects of statins

Researchers writing in JAMA have identified two common single-nucleotide polymorphisms (SNPs) that seem to attenuate the cholesterol-lowering effects of statins.Dr Paul Ridker and colleagues, from the Brigham and Women's Hospital in Boston, screened the DNA of 1536 individuals treated with pravastatin (40 mg/d) for 148 single-nucleotide polymorphisms within 10 candidate genes related to lipid metabolism. Variation within these genes was then examined for associations with changes in lipid levels observed with pravastatin therapy during a 24-week period.Investigators found two closely linked SNPs that were significantly associated with a difference in the change in lipid response to pravastatin. Both of these SNPs were in the gene coding for 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase gene - SNP 12 and SNP 29- encoding for the target of statin therapy. The researchers report that for those with a single copy of SNP 12 or SNP 29 in the HMG-CoA reductase gene, there was a 22% smaller reduction in total cholesterol and a 19% smaller reduction in LDL cholesterol. No other SNPs were associated with the lipid response to pravastatin, the investigators point out."We recognize that these data have considerable pathophysiological interest and provide strong clinical evidence that there may be promise in the concept of 'personalized medicine' and the use of genetic screening to target certain therapies," the researchers state.Further studies are needed to determine if the refractory hypercholesterolemia observed in patients with either SNP can be overcome with higher statin doses or with a nonstatin agent, they conclude.Reference...