Boston - July 2004, Harvard Medical School affiliate Brigham and Women's Hospital - While millions of Americans use "statin" drugs to lower cholesterol and prevent heart disease, doctors have known that not all patients receive similar benefits. In a comprehensive search for genetic influences on cholesterol reduction, researchers at the Brigham and Women's Hospital (BWH) have found a common genetic variant that appears to make statin therapy significantly less effective in certain patients. The genetic variant occurred in seven percent of the population studied. In an evaluation of more than 1,500 people receiving the cholesterol lowering medication pravastatin, the researchers found a common genetic variant in the molecular target for statin therapy known as HMG CoA reductase. Compared to individuals without the genetic variant, those who were affected had a 22 percent smaller drop in total cholesterol and a 19 percent smaller drop in LDL or "bad" cholesterol while on statin therapy. This effect was present among those with and without known heart disease and was large enough in magnitude to have importance at a public health level. "What is so interesting is that of a large number of genes studied, the most important genetic variation turned out to be in the gene encoding the actual target for statin therapy," said study lead author Daniel Chasman, PhD of the Harvard Medical School. The study results were published in the June 16, 2004 issue of the Journal of the American Medical Association. The new findings are of particular importance for drug development and the emerging field ofÊ "pharmacogenetics" where it has been anticipated that inherited differences between patients might provide a method to improve care. The data are also important as statin drugs are among the most widely used agents with over 20 million patients treated in the United States alone. "Our data show what many physicians have long suspected, namely that genetic differences in drug targets can impact upon an individual's drug response," said Paul Ridker, MD, director of the Center for Cardiovascular Disease Prevention at the BWH. "The new data also reflect the potential for translating knowledge of genetic differences into clinical medicine. The hope of pharmacogenetic studies like ours is ultimately to provide the right drug at the right dose to the right patient." The genetic variation identified may provide clues for the development of new drugs to lower cholesterol, and research is already ongoing to better understand how the genetic variant affects drug response. The authors caution that additional studies will be needed not only to confirm these effects but also to determine if they can be offset by altered dosing or use of different non-statin medications. "Our observations do not suggest that doctors should change the way statins are prescribed or how cholesterol should be managed," Chasman pointed out. "Rather, our results demonstrate the genetic complexities of drug response and the promise of personalized medicine. People are different in many ways, including how they respond to statin therapy."