Setting the Stage for Personalized Medicine
New Association Identified between Statin Efficacy and Single Nucleotide Polymorphisms in the HMGCR Gene
In a new study published in Circulation, CHORI senior scientist Ronald Krauss, MD, and his colleagues identified a novel gene variation that provides one more piece of the puzzle in developing personalized medicine. Using genomic sequencing on the gene that codes for hydroxymethyl glutaryl coenzyme A reductase (HMGCR), the enzyme targeted by statins, Dr. Krauss hoped to find clues as to how to make that group of cholesterol-lowering drugs more effective.
“In the current study we found a series of single neucleotide polymorphisms, or SNPs in the HMGCR gene that collectively resulted in a lower statin response,” says Dr. Krauss.
While statins have had a revolutionary impact on current cholesterol management, two-thirds of individuals on treatment remain at high risk for cardiovascular disease, leaving significant room for improvement.
"A 30 percent reduction in risk is quite an important effect on the health of this country, but our goal is to try to understand how we might improve treatment even more by identifying the factors that lead to greater improvement in risk in some populations, but not in others," Dr. Krauss explains.
Statins work by blocking the action of HMGCR, the most critical enzyme involved in the pathway for cholesterol production in the body, making the HMGCR gene a natural target for genomic studies geared at better understanding what genetic influences might be at play in determining the efficacy of statin response.
"What we found was a small but significant difference between African Americans and Caucasians in the amount of cholesterol lowering that was achieved, which corresponded with a series of SNPs also found only in a small subset of African Americans that could collectively account for that lowered statin response," Dr. Krauss explains.
While the difference is not large enough to suggest that African Americans as a whole won't benefit from statin treatment, it does provide evidence that genes can significantly impact on statin efficacy. When more such effects are identified and harnessed, the era of personalized medicine, in which patients can be treated with different kinds or doses of drugs based on their genetic differences, will move into high gear.In addition, Dr. Krauss also found that the very same SNPs that were associated with a lowered statin response were responsible for a lowered level of low density lipoproteins (LDLs), or bad cholesterol as well - but under normal baseline conditions and before treatment with statins.
Tuesday, May 17, 2011 8:19 AM