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Harbinger of the Future
CHORI Scientist Invited to Write Lancet Commentary

"We now have these powerful genomic tools that allow for the scanning of the whole genome for a trait that, although more subtle, could still have significant effects on heart disease risk."

As someone who has spent many years pioneering research in cholesterol and low-density lipoprotein (LDL) metabolism, and is now breaking new ground in the area of genomics and LDL, CHORI senior scientist Ronald Krauss, MD, was an ideal choice for the February commentary in Lancet. Dr. Krauss, also a member of CHORI’s Center for the Prevention of Obesity, Cardiovascular Disease & Diabetes, brought considerable knowledge to bear on the subject of genome-wide scanning for single-nucleotide polymorphisms, or SNPs, related to genetic disorders of lipoprotein metabolism.

In the Lancet commentary, Dr. Krauss reviews a number of recently published studies identifying certain SNP associations with LDL cholesterol and other lipids and lipoproteins, collectively using these results to elucidate the benefits of genomic cholesterol studies.

"If we can discover new genetic influences or traits associated with LDL cholesterol and other heart disease risk markers, it could help to identify the subgroup of individuals in whom this particular genetic component could be addressed more specifically by more individualized treatment approaches," explains Dr. Krauss.

Although statins, which are the most widely used drugs for cholesterol lowering are hugely successful in reducing heart disease risk, two thirds of individuals on treatment remain at high risk.It is this group for whom genomic testing could prove the most beneficial.

As Dr. Krauss points out, "The information we can get from genomic studies can serve as a basis for developing new drugs that could target the lowering of LDL cholesterol in the many individuals who don't respond adequately to statin treatment and could benefit from alternative approaches."

Although Dr. Krauss acknowledges that there are some limitations of genomic studies to date, such as the predominance of people of European descent as study participants, and the reliance on combined cohort populations for statistical power, there is no doubt that genomic techniques are the harbinger of the future.

"It's the beginning of what promises to be an even more wide-scale approach to understanding the basis of human disease and for developing new treatment protocols."
"The next dimension to all of this is going to take us from scanning for polymorphisms to actually being able to sequence large pieces of the genome, and eventually the whole genome, in order to learn about every single marker across an entire genome in any substance being studied. That is the next generation of analysis," says Dr. Krauss.

While it is already known that humans have many, many genetic markers in common across individuals from different populations and every corner of the globe, there are also places in which the genetic fingerprints diverge, which could provide critically important information. With the genomic-wide sequencing that Dr. Krauss sees as the next research horizon, scientists like Dr. Krauss would be able to identify those differences, which could lead to greater treatment specificity and achieving the reality of personalized medicine.
"Genomic scanning is still uncharted territory for most disease conditions, so this is really the age of discovery where we're able to find those landmarks that will steer us in the right direction," says Dr. Krauss.

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Tuesday, May 17, 2011 8:19 AM

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