Research from CHORI scientist reveals genetic link between cholesterol-lowering statin drugs and potentially harmful effects on muscles
August 28, 2013, Oakland, CA – A particular gene may influence the risk for a rare but potentially severe side effect of cholesterol-lowering statin drugs – myopathy, or muscle damage, concluded a study by Dr. Ronald Krauss of Children’s Hospital Oakland Research Institute (CHORI), along with a team of investigators from multiple institutions. Published this week in the journal Nature, the groundbreaking study demonstrates that differences in susceptibility to myopathy from statin treatment may be related to a genetically determined variation in the expression of the gene glycine amidinotransferase – or GATM.
Statins are widely prescribed to lower cholesterol levels and cardiovascular disease risk, but can in some individuals lead to muscle pain or weakness – and in very rare cases - to serious muscle breakdown. Past studies have identified genetic traits associated with this side effect, but these traits account for a very small proportion of overall risk. In this latest study, however, researchers identified a much more common genetic variant that regulates statin-induced expression of GATM, a gene known to have a key role in production of creatine - a source of energy in muscles. The authors investigated the association of the GATM variant with myopathy in two separate populations of statin-treated patients, and in both groups, there was a 40% lower risk of myopathy among individuals who carried the variant.
In another critical finding, the study’s researchers demonstrated that the GATM gene has a direct effect on cholesterol metabolism. The results suggest that GATM is a central and previously unrecognized link between cholesterol lowering from statins and susceptibility to statin-induced myopathy.
“Our research has shown that an investigation of basic cellular mechanisms influenced by statins can lead to identification of genetic variants that contribute to clinically important differences in response to statin treatment,” concludes Dr. Krauss. “My colleagues and I are carrying out further studies to determine the mechanism for the GATM genetic effect, which may lead to the identification of additional markers for assessing risk of statin-induced myopathy.”
About Children’s Hospital & Research Center Oakland:
Children’s Hospital & Research Center Oakland is a premier, not-for-profit regional medical center for children in Northern California. Children’s Hospital Oakland is a national leader in many pediatric specialties and sub-specialties including hematology/oncology, neonatology, cardiology, orthopedics, sports medicine, and neurosurgery. The hospital is one of only two solely designated California Level 1 pediatric trauma centers with the largest pediatric inpatient critical care unit in the region. Children’s Hospital has 190 licensed beds, 201 hospital-based physicians in 30 specialties, more than 2,700 employees, and an annual operating budget of more than $350 million. Children’s is also a premier teaching hospital with an outstanding pediatric residency program and a number of unique Pediatric subspecialty fellowship programs. To learn more about Children’s Hospital & Research Center Oakland, go to www.childrenshospitaloakland.org.
Research efforts at Children’s Hospital & Research Center Oakland are coordinated through Children’s Hospital Oakland Research Institute (CHORI). CHORI’s internationally renowned biomedical research facility brings together seven centers of excellence that are devoted to clinical and basic science research to treat and prevent disease. CHORI has approximately 300 staff members and an annual budget of about $50 million. The National Institutes of Health is CHORI’s primary funding source and CHORI is ranked among the nation’s top 10 research centers for NIH funding to children’s hospitals. The institute is a leader in translational research, bringing bench discoveries to bedside applications. These include providing cures for blood diseases, developing new vaccines for infectious diseases and discovering new treatment protocols for previously fatal or debilitating conditions such as cancers, sickle cell disease and thalassemia, diabetes, asthma, HIV/AIDS, pediatric obesity, nutritional deficiencies, birth defects, hemophilia and cystic fibrosis. For more information, go to www.chori.org.