Study Casts Doubt On Value Of Genetic Testing For Familial Hypercholesterolemia Reply

new study published online in the Lancet suggests that one of the main screening plans that relies on genetic tests will fail to identify a substantial portion of people with familial hypercholesterolemia.

Investigators from the UK and Belgium analyzed DNA from several cohorts of FH and non-FH patients. Their chief finding was that a large percentage of FH patients did not have one of the single genetic mutations known to cause FH. Instead, these patients, termed “polygenic,” were found to have variants in multiple genes, each of which had a small LDL-raising effect, but when combined resulted in LDL levels similar to those in people with known FH mutations.

According to one cholesterol expert: 

The take home is that genetic screening is not a panacea and that screening based on fasting ipids makes most sense. Indeed, I never understood genetic screening for this disease anyway, since the phenotype (hypercholesterolemia) is what kills people, not the genotype, the phenotype is readily available with a blood test, the disease is not immediately fatal (It takes years to develop), and treatment is based on the numbers. It is like asking for a gene test fro sickle cell anemia. You can look at blood and make the diagnosis.

Click here to read the complete story on Forbes.

 

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Proof-of-Concept for Bedside Rapid Genotyping Test of CYP2C19 1

A new point-of-care test can rapidly identify people with a common genetic variant associated with impaired clopidogrel function. The authors claim that this is the first study to demonstrate the feasibility of delivering a genetic test at bedside.

In an article published online in the Lancet, Jason Roberts and colleagues report on a new point-of-care test that can identify people who have a common variant of the CYP2c19 gene associated with reduced clopidogrel effectiveness. In their “proof-of-concept” study, 200 patients undergoing PCI were randomized to standard therapy with clopidogrel or to the new test. Patients found to have the CYP2C19*2 allele received prasugrel instead of clopidogrel.

Each group had 23 patients who carried at least one CYP2C19*2 allele. Among these patients, no patients in the test group, and 7 patients (30%) in the control group, were found to have high on-treatment platelet reactivity (PRU) after 1 week of treatment. At 7 and 30 days, there were no ischemic events in either group and no significant differences in major or minor bleeding.

The investigators write that their study “confirms the potential clinical benefits associated with a personalised approach to antiplatelet treatment with selective use of P2Y12 inhibitors in patients at increased risk of adverse events with clopidogrel,” but they also noted that the “major limitation” of their study “was use of a surrogate endpoint to assess clinical efficacy.”

In an accompanying comment, Amber L Beitelshees notes that “.”many clinicians do not know what action to take, if any” until the completion of large trials that are in progress. Earlier studies testing the platelet hypothesis may have failed, she says, because new evidence suggests that benefits of genotyping or platelet function tests may be confined to the PCI population. The new rapid genotyping test will make it easier “for incorporation into clinical care in the catheterisation laboratory.”
Click here to read the Lancet press release…