Response to Statins: It's in the Genes

Statins effectively lower LDL cholesterol levels in many patients, However, on the individual level, some patients do not respond with the expected 40% to 55% reduction in cholesterol levels. Genetic variation may be the cause.

Globally, statins are the most commonly prescribed class of drug. The October 2014 issue of Nature Communications includes a study conducted to determine what accounts for the variability in interindividual response to statins. Statins effectively lower LDL cholesterol levels in patients who participated in large studies. On the individual level, some patients do not respond with the expected 40% to 55% reduction in cholesterol levels. Genetic variation may be the cause.

The research discussed in this article was performed by a team of 59 researchers at leading research institutions from around the world. They performed pharmacogenetic meta-analysis of genome-wide association studies (GWAS) addressing the LDL cholesterol response to statins. Their study population included more than 18,000 statin-treated subjects and an additional 22,000 statin recipients to validate promising signals.

This meta-analysis combined the results of 6 randomized controlled studies and 10 observational studies, creating a subject pool of more than 40,000 participants. The large number of patients increases the validity of their findings. Their data also included a variety of statins and statin doses. From this they determined that SLCO1B1 variants are highly dependent on the specific statin prescribed and the dose used.

The researchers identified two loci, SORT1/CELSR2/PSRC1 and SLCO1B1, not previously identified in GWAS. They also confirmed the previously described associations with APOE and LPA. These findings advance the knowledge of the statin response’s pharmacogenetic architecture. By expanding our understanding of the genes and pathways associated with statin response variation, researchers may be able to improve the use of cardiovascular drug therapy, allowing clinicians to select the most appropriate drug therapy based on each patient’s genetic composition. Many researchers hope that eventually clinicians will employ pharmacogenetics to pre-screen and identify subjects susceptible to adverse drug reactions.