![\"Statin\"](\"https:\/\/blogs.nature.com\/spoonful\/files\/2013\/08\/Statin-208x300.jpg\" "\\"Statin\\"")
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The global market for statins has reached heart-stopping proportions, registering at almost $20 billion in 2012<\/a>. In the US, one out of every four adults<\/a> over the age of 45 is on statins, making these medications one of the leading types prescribed. The drugs work by lowering the liver\u2019s production of low-density lipoproteins, also known as \u2018bad\u2019 cholesterol, which form the artery-clogging plaques that can lead to heart attack. But statins can cause significant side effects<\/a>, ranging from sleeplessness to an increased risk of type 2 diabetes<\/a> and potential liver damage.<\/p>\n One of the most common side effects is muscle pain and injury, which afflicts up to 38%<\/a> of people taking statins. Now, researchers have hit upon a new gene variation that could explain why some individuals are less prone to this type of adverse reaction to such drugs.<\/p>\n The scientists themselves sound surprised at the discovery. \u201cWe weren\u2019t focused on finding the cause of the muscle damage,\u201d says Ronald Krauss<\/a>, director of atherosclerosis research at Children\u2019s Hospital Oakland Research Institute in California and lead author of the new study, which appears online today<\/a> in Nature<\/i>. \u201cWe were looking at cell lines from patients on statins to discover new gene variants and we found one that affects how the drug works.\u201d<\/p>\n It\u2019s not the first effort to look at statin side effect risks though the lens of genetics. Five years ago, researchers found<\/a> that individuals on high doses of simvastatin\u2014a statin marketed as Zocor by New Jersey-based Merck\u2014who also carried a specific variant in the SLCO1B1<\/i> gene were fifteen times more likely to have muscle pain and injury, also known as myopathy. Based on these findings, which also correlated with markedly higher blood levels of a muscle damage biomarker, the US Food and Drug Administration set new guidelines<\/a> recommending alternative medications for patients who need more than 40 milligram a day of simvastatin to lower their cholesterol.<\/p>\n In the new study, Krauss and his colleagues screened cultures of white blood cells, taken from 480 different patients on simvastatin. The researchers examined more than 10,000 genes, and narrowed their focus on four genes that specifically showed the most robust changes in activity when the cells were exposed to simvastatin. Of that quartet of genes, they selected the glycine amidinotransferase (GATM<\/i>) gene for further study because it codes for an enzyme that makes creatine, a molecule that helps muscle cells store energy.<\/p>\n Protective effect<\/strong><\/p>\n To test whether or not GATM<\/i> was associated with muscle damage, the scientists compared cells from 72 people taking statins who reported myopathy against cells taken from 220 people on statins who didn\u2019t have muscle damage. They discovered that only 40% of people on statin prescriptions who had muscle problems carried the protective variant called rs9806699. By comparison, 49% of the people on statins who didn\u2019t report any muscle ailment had at least one copy of the GATM<\/i> variant. Researchers found similar results when they looked for that same variant in cells from a further 100 participants who reported myopathy as a side effect in a different statin study of more than 12,000 people. Overall, about 25-30% of the subjects included in these studies had at least one copy of the GATM<\/i> variant. However, these investigations only included participants of European descent; researchers remain unsure of how frequently this gene is found in the general population.<\/p>\n \u201cMore work needs to be done,\u201d notes Lara Mangravite<\/a>, first author on the paper and a biologist at Sage Bionetworks in Seattle. \u201cWe see that GATM<\/i> has a role in muscle biology, but we need to know how it changes the cholesterol production in the liver, which then affects the wellbeing of the muscle.\u201d<\/p>\n Krauss speculates the GATM <\/i>variant may be protecting people by suppressing the statin-induced ramp-up of creatine production, thereby lowering the concentration of this energy-producing molecule and perhaps reducing muscle cells\u2019 risk of being over-stressed.<\/p>\n Even though the effect of the GATM<\/i> variant probably isn\u2019t big enough to be thinking about a clinical test for the gene before prescribing statins, it\u2019s still an important study, according to\u00a0Alan Shuldiner<\/a>, director of the Program in Personalized and Genomic Medicine at the University of Maryland School of Medicine in Baltimore. \u201cWe\u2019re seeing that more drug\u2013gene effects have multiple genes involved and now we have two genes on the map for statins,\u201d he says.<\/p>\n But, ultimately, a person\u2019s genetic predisposition to muscle problems from statins might not influence whether they receive such drugs. \u201cThis is an impressive finding from a research perspective, but what next? Clinically there\u2019s still no substitute for statins,\u201d says\u00a0pharmacogenetics researcher Julie Johnson<\/a>, dean of the University of Florida College of Pharmacy in Gainesville.<\/p>\n Image by Lightspring via Shutterstock.com<\/a><\/i><\/p>\n","protected":false},"excerpt":{"rendered":" The global market for statins has reached heart-stopping proportions, registering at almost $20 billion in 2012. In the US, one out of every four adults over the age of 45 is on statins, making these medications one of the leading types prescribed. The drugs work by lowering the liver\u2019s production of low-density lipoproteins, also known as \u2018bad\u2019 cholesterol, which form the artery-clogging plaques that can lead to heart attack. But statins can cause significant side effects, ranging from sleeplessness to an increased risk of type 2 diabetes and potential liver damage. Read more<\/a> Continue reading