A large analysis of over 40,000 individuals undergoing statin treatment has revealed two new genetic variants that may affect how low density lipoprotein (LDL) cholesterol responds to statin therapy. The study, published in Nature Communications, provides further insights into the genetic basis of drug response.
Statins have been shown to lower LDL cholesterol levels by up to 55% and are therefore highly effective in the management and prevention of cardiovascular disease. Despite this success, however, patient response can vary widely and this variation is known to have a genetic component.
Mark Caulfield and colleagues analysed data from six randomised clinical trials and ten observational studies to look for genetic variants influencing patients’ response to statins. They validated their findings in a further 22,318 individuals and found two new genetic variants that significantly affected the degree to which LDL cholesterol was lowered during treatment.
One variant, located near the sortilin gene (a gene already associated with lipoproteins) was shown to enhance statin response. In contrast, the second variant, thought to have a role in the uptake of statins by the liver, decreased the effects of the drug. Taken together, these findings may increase our understanding of the biological mechanisms underlying LDL cholesterol response to statin therapy.