Illumina, Inc. has announced that it has signed an agreement with Children's Hospital Oakland Research Institute (CHORI) to provide reagents and instrumentation for a study aimed at determining the impact of single nucleotide polymorphisms (SNPs) on individual response to statins, a widely used class of cholesterol-lowering drugs.
The study is being carried out as part of the NIH-funded research program, Pharmacogenomics and Risk of Cardiovascular Disease (PARC).
At the end of the current five-year grant period, PARC aims to have identified critical genetic determinants of response to statin therapy that could be used by health care providers to ensure the best cardiovascular outcome and the lowest risk of treatment for each patient.
The PARC research program is led by Principal Investigator Ronald Krauss, M.D, Senior Scientist and Director of Atherosclerosis Research, at CHORI.
The experimental plan divides the study into four sequential phases to ensure adequate statistical power and minimize the risk of false positive results in identifying the most informative SNPs associated with statin response and clinical cardiac endpoints.
Statin response phenotypes to be evaluated include levels of LDL and HDL and their subfractions, indices of cholesterol synthesis and absorption, and inflammatory markers.
The study also aims to identify SNPs associated with statin-related myopathy, an uncommon side effect characterized by damaged muscles.
Sample genotyping for all phases will be performed in Dr. Nickerson's laboratory with a fully automated Illumina BeadStation system and four leased Illumina BeadArray Readers to accommodate the sample throughput planned in the project schedule.
Samples will be drawn from large clinical trials previously carried out by investigators in PARC and other research programs that have tested effects of the statin drugs simvastatin, pravastatin, rosuvastatin and atorvastatin on laboratory and clinical measures of cardiovascular disease risk.
Phase I will involve whole-genome association analysis of over one thousand clinical samples using the Sentrix® Human-1 BeadChip and a follow-on Sentrix HumanHap-1 BeadChip that can query over 250,000 TagSNPs derived from the International HapMap Project.
The study will use Illumina's Infinium™ assay, which enables the intelligent selection and analysis of virtually any SNP in the genome, providing coverage and multiplex levels that are limited only by the number of features on the BeadChip.
Infinium performance, as measured by call rate, accuracy and reproducibility, is comparable to Illumina's GoldenGate® assay protocol, the gold standard of the HapMap Project.
Following confirmatory analysis of Phase I findings on additional clinical samples and cohorts, subsequent phases will systematically evaluate haplotype blocks, specific haplotypes within each block, and SNPs within those haplotypes to identify the most informative variants and those that have causal association with clinical phenotypes.
Over 10,000 samples will be tested in the latter phases of the project, which will employ fine mapping techniques using Illumina's GoldenGate assay protocol, custom panels of SNP markers, and Sentrix Universal Array Matrices.
Commenting on the study, Dr. Krauss stated, “This project will be among the very first to fully leverage HapMap data to streamline genome-wide analysis.”
“The new genotyping tools will enable the PARC team to economically conduct large-scale, multicohort-designed experiments and deliver results of meaningful value to the clinic.”
“We look forward to working with Illumina on this project, the design of which we believe will serve as a model for studying the pharmacogenomics of a wide range of diseases.”
According to Jay Flatley, Illumina President and CEO, “We're tremendously excited to work with the PARC investigators and delighted that our genotyping solutions will contribute to this seminal study.”
“This is the kind of research that will demonstrate the benefits of pharmacogenomics and fuel the evolution toward personalized medicine.”