NEW YORK (Reuters Health) - Researchers have identified two common single-nucleotide polymorphisms (SNPs) that seem to attenuate the cholesterol-lowering effects of statins, according to a report published in the June 16th issue of the Journal of the American Medical Association.
Dr. Paul M. Ridker, from Brigham and Women’s Hospital in Boston, and colleagues screened the DNA of 1536 pravastatin users for 148 SNPs in 10 genes involved in lipid metabolism. The drug’s effect on cholesterol levels was then determined over a 24-week period.
The two SNPs linked to reduced efficacy both involved HMG-CoA reductase, the enzyme blocked by pravastatin. The presence of either SNP, in the heterozygous state, attenuated the reduction in total cholesterol and LDL cholesterol by around 20%. Neither SNP seemed to affect changes in HDL cholesterol levels.
No other SNPs were associated with the lipid response to pravastatin, the investigators point out.
“We recognize that these data have considerable pathophysiological interest and provide strong clinical evidence that there may be promise in the concept of ‘personalized medicine’ and the use of genetic screening to target certain therapies,” the researchers state.
Further studies are needed to determine if the refractory hypercholesterolemia observed in patients with either SNP can be overcome with higher statin doses or with a nonstatin agent, they add.
In a related editorial, Dr. Wylie Burke, from the University of Washington in Seattle, and Dr. Susanna B. Haga, from The Center for the Advancement of Genomics in Rockville, Maryland, comment that “this study is the first to demonstrate the impact of genetic variation in the HMG-CoA reductase drug target for this popular class of drugs, justifying the need for further study to validate and perhaps translate these findings into the clinical setting.”
Source: JAMA 2004;291:2821-2827,2869-2871. [ Google search on this article ]
MeSH Headings:Polymorphism, Single NucleotideCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
