With individual customers currently few and far between, some companies have fashioned themselves into research-ready firms, able to help scientists sequence and interpret genetic information for their studies.
Many clinical tests for single mutations, however, have already been having a meaningful impact for years. Testing for certain known genetic mutations that cause different kinds of breast cancer, for example, can help tell oncologists what kinds of treatment will be most effective—and least harmful—to the patient. But with all of the head-scratching over full-genome scan fallibilities, these single-gene mutation tests are "the kind of things people are losing sight of," Bernhardt says.
Despite a bumpy start and uncertain regulatory future, many who follow the consumer genomic testing industry are optimistic: Boyce projects that when electronic medical records become more prevalent, people will be able to add their genomic scans, which could help them and their doctors manage personal health; but it could also be a boon to researchers if individuals make them available for study. With millions of health records and related genomes available researchers might eventually have access to study populations of unprecedented size, breadth and depth, in turn making individual genomic-based predictions more accurate, reliable and perhaps more appealing.
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Add CommentI agree with the general content of the article, however I will suggest that attempting to define the "success of gene testing" in concrete terms is by it's very nature inherently flawed. We all want our healthcare professional to provide us with definitives. Give my problem a name and an ICD9 code. However human kind represents a dynamic, multi-factorical complexity such that the best we can provide is an increase or decrease in the probability of an outcome. Being able to take the complexity of analysis and reduce it to a reasonable analysis is the challenge. Any analysis needs to be in the hands of the TRAINED healthcare professional, not the consumer.
Reply | Report Abuse | Link to thisI will suggest that the area of drug metabolism, gene analysis has the probability to improve the status quo. A study last year by MEDCO reported that $145 Billion of the $292 Billion spent on prescription drugs DID NOT WORK. The MEDCO findings indicate that the introduction of a drug into a patient protocol is at best, a toss of the coin in terms of it's probability of meeting the drug's intended target or goal.
Prescription drugs that utilize hepatic pathways have been defined. I will further suggest that KNOWING the degree that a drug pathway is compromised provides for an INFORMED decision by the healthcare professional. The group of genes called CYPs (Cytochrome P450s) represent the intersection in the pathway for many drugs. CYP450s serve a dual purpose, they are part of the pathway of elimination (metabolizing) of drugs, both prescription and OTC however in some instances these genes are needed to activate the drug (Pro-drug). Some foods, nutrients, OTC drugs, exotoxins and other prescription drugs can and do impact how these genes express (produce the enzyme/protein). In effect these other substances have a probability of compromising the elimination or activation of drugs that use CYP pathways, even if the gene is "normal" in function (EM - extensive metabolizer).
The diversity of function in drug metabolizing genes is an extremely important variable to consider in optimizing a patients drug protocol. CYP genes vary in function from poor metabolizers (PM - NO FUNCTION) to ultra-rapid metabolizers (URM - up to 13 duplicates) of the same gene. Knowing the function of a CYP is an important factor to consider. In my experience in analyzing this group of genes for patients, most drugs use more than one pathway for metabolism. So complexity is the norm and the possible combinations of variables exceeds even the brightest of minds.
The pharmacologic and toxic effects of certain drugs are exaggerated in a significant percentage of the population due to a heritable deficiency in CYP 450 enzymes (Tucker, 1994; Meyer, 1994; Smith et al., 1998). The two major polymorphically (many forms) expressed CYP450 enzymes are CYP2D6 and CYP2C19. The incidence of the poor-metabolizer genotype varies among different ethnic groups. Five to 10 percent of individuals in Caucasian populations are of the PM (no function) CYP2D6 genotype and have deficient metabolism of debrisoquine (an antihypertentive drug metabolized by CYP2D6) and over 25 other drugs. However, less than 1 percent of Japanese subjects are defective in CYP2D6 activity. In contrast, 20 percent of Japanese subjects are poor metabolizers of S-mephenytoin (an anticonvulsant metabolized by CYP2C19), whereas less than 5 percent of Caucasians are so affected (Kaneko et al, 1999).
Significant improvements in patient outcomes and sharp reductions in the cost of ineffective medications and the effects of ADRs and ADEs can be achieved by considering the effects of genetic variation and of other drugs, supplements and foods in a patients protocol.
Several examples follow.
Drug-gene interaction: Warfarin therapy
Warfarin is an anticoagulant commonly used to prevent and control blood clots, but it is complicated to use because the optimal dose varies greatly among patients. If the dose is too strong, the risk of serious bleeding increases and if the dose is too weak, the risk of stroke increases. In a 2006 study, the AEA-Brookings Joint Center for Regulatory Studies estimated that formally integrating genetic testing into routine Warfarin therapy could allow American users to avoid 85,000 serious bleeding events and 17,000 strokes annually. They also estimated integrating genetic testing into Warfarin therapy could save $1.1 billion annually.
Drug-gene and drug-drug example: Plavix and Protein Pump Inhibitors
Plavix (clopidogrel) is the second largest selling drug in the world. It is commonly prescribed to reduce the risk of blood clots and potentially fatal heart attacks in patients who have received stents to open clogged coronary arteries. Researchers have found that patients with variations in the gene cytochrome CYP2C19 have a 3.6 times greater risk for major adverse cardiovascular events such as death, heart attack, and stroke; the risk was greatest in CYP2C19 poor metabolizers.
Recent studies have also created confusion about the appropriate use of Plavix and Proton Pump Inhibitors (PPIs) a group of drugs including Prilosec, Prevacid and Nexium, that produce a pronounced and long-lasting reduction of gastric acid production. The Medco Outcomes Study, a retrospective analysis of 16,690 patients taking clopidogrel for a full year following coronary stenting revealed that patients who also took a PPI for an average of nine months experienced a 70% increase in the risk of heart attack or unstable angina, a 48% increase in the risk of stroke or stroke-like symptoms, and a 35% increase in the need for a repeat coronary procedure. The proposed mechanism is that PPIs inhibit CYP2C19-mediated metabolic bioactivation of clopidogrel into its active ingredient. Clopidogrel is a pro-drug that requires the enzyme to take it's active form.
Drug-food example: grapefruit and common statins
Statins are the most widely prescribed cholesterol-lowering medications. Grapefruit contains the compound bergamottin, which interacts with the cytochrome P-450 and P-glycoprotein enzyme systems. These enzyme systems are responsible for breaking down statins, as well as other drugs, into more usable chemicals and transporting them in the body. When a person consumes grapefruit or grapefruit juice at or around the time of their statin dose, bergamottin prevents the enzyme systems from breaking down the drug, causing high amounts of the statin drug to accumulate in the body. This can cause a variety of very dangerous health problems, such as liver damage or severe muscle and kidney damage.
So the bottom line is, there is NO simple solution. The only way for the healthcare professional to determine the viability of a drug working as intended is to KNOW how this group of CYP genes function and what other substances have influence on them. By having an understanding of how the pieces of the puzzle interact, and how our own unique puzzle is laid out, can the healthcare professional have a probability of decreasing a negative effect (side effect, ADR or ADE). Unfortunately most physicians were not trained in pharmacogenomics and the analysis is time consuming. The result is that the probability of a physicians "guess" being correct is not better than a toss of a coin. Ever heard the statement by your physician "let's try this, and if it doesn't work we will try something else?" The future in drug protocol effectiveness is based on Personalized Medicine, and in this case, Pharmacogenomics is the key to that reaching that end.
Scratch that, I'm blind and didn't spot that the link was in the text, but still citing it at the end clearly would be nice.
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