Skip to main content
Premium Trial:

Request an Annual Quote

Study Links Two SNPs to Reduced Statin Efficacy

Premium

Two common SNPs have been linked to significantly reduced efficacy of the drug pravastatin, in a new study published in the June 16 edition of the Journal of the American Medical Association.

In the study, Paul Ridker and colleagues from Harvard Medical School collaborated with a team from Variagenics (now part of Nuvelo) led by Daniel Chasman, to genotype a population of 1,536 individuals who received pravastatin as part of a clinical trial. This statin drug is manufactured by Bristol-Myers Squibb, and is prescribed, under the name Pravachol, for the lowering of cholesterol

The trial, the Pravastatin Inflammation/CRP Evaluation, or PRINCE trial, was a randomized, controlled cohort study supported by Bristol-Myers Squibb that examined the effects of 40 mg of pravastatin per day on lipid and inflammatory biomarkers. Participants in this trial came from around the US.

The research team looked at 148 SNPs in 10 candidate genes that have been previously shown to be involved in synthesis, absorption, and transport of cholesterol, and statin metabolism. Of these, they found two SNPs in the HMG-CoA reductase gene that were significantly associated with reduction in cholesterol levels among the participants. The HMG-CoA reductase gene encodes the target enzyme for pravastatin.

Individuals who were heterozygous for either SNP had a 22 percent smaller reduction in total cholesterol levels, and a 19 percent smaller reduction in low-density-lipoprotein cholesterol (known as “bad” cholesterol).

These associations remained robust even after the researchers performed regression analysis for lipid level, sex, hormone therapy status, age, and age squared. The associations also became stronger after the population was stratisfied for ethnicity, with the association more significant in whites (who made up 88.7 percent of the study population) than non-whites.

The authors cautioned that this study does not apply to all statins, does not allow dose-response effects to be evaluated, and requires independent confirmation. But they acknowledged the significance of the findings. “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,” they wrote. “The abolute difference in total cholesterol reduction associated with the HMG-CoA reductase genotype in our data was 9 mg/dL, an effect large enough to affect health on a population basis. Future studies must determine whether this difference can be offset by dose adjustment or the choice of an alternative nonstatin lipid-lowering therapy.”

—MMJ

Filed under

The Scan

Breast Cancer Risk Related to Pathogenic BRCA1 Mutation May Be Modified by Repeats

Several variable number tandem repeats appear to impact breast cancer risk and age at diagnosis in almost 350 individuals carrying a risky Ashkenazi Jewish BRCA1 founder mutation.

Study Explores Animated Digital Message Approach to Communicate Genetic Test Results to Family Members

In the Journal of Genetic Counseling, the approach showed promise in participants presented with a hypothetical scenario related to a familial hereditary breast and ovarian cancer syndrome diagnosis.

Computational Tool Predicts Mammalian Messenger RNA Degradation Rates

A tool called Saluki, trained with mouse and human messenger RNA data, appears to improve mRNA half-life predictions by taking RNA and genetic features into account, a Genome Biology paper reports.

UK Pilot Study Suggests Digital Pathway May Expand BRCA Testing in Breast Cancer

A randomized pilot study in the Journal of Medical Genetics points to similar outcomes for breast cancer patients receiving germline BRCA testing through fully digital or partially digital testing pathways.