News Feature | March 17, 2014

Statin Side Effects Linked To Cholesterol-Related Locus

By Liisa Vexler

A group of researchers from the University of Chicago, Seattle's Sage Bionetworks, the Children's Hospital Oakland Research Institute, and others have located a new cholesterol-related locus which links to a risk of side effects of the muscles for people taking statin drugs.  Array-based gene expression patterns in the cells of 500 people were looked at in a trial involving simvastatin. Tests went on to locate a statin-related expression quantitative trait locus, also known as eQTL, found on chromosome 15, affecting the expression of the enzyme-encoding gene GATM.

The statin effect is a type of muscle weakness known as myopathy, a side-effect experienced by some patients. Matthew Stephens of the University of Chicago and Ronald Krauss of the Children's Hospital Oakland and colleagues commented, “this approach has led to the identification of GATM as a genetic locus associated with statin-induced myopathy," they noted, "and as a potential link between cellular cholesterol homeostasis and energy metabolism." The experiment among participants sought to tease out genetic variants with links to statin response and risk. The researchers looked specifically at transcriptional profiles in the cells they studied, for people of Euro-American backgrounds who took the drug and who did not.  A detailed look at data for 72 people taking statin drugs who experienced myopathy and those that were unaffected (totalling 220) was undertaken and it was found that those with a less common version of the GATM eQTLtypes did not develop myopathy as often.  The research to look at statin-induced myopathy was further considered for another 100 people who signed up for a study named SEARCH (Study of Additional Reductions in Cholesterol and Homocysteine).  Findings of the study, which looked at cholesterol levels and the relationship to the presence of the GATM gene, reinforced the gene’s role in cholesterol related processes.