Connection Between Epigenome, Selective Mutability, Evolution, and Human Disease
Li, Harris et al., PLoS Genetics
Researchers at the Baylor College of Medicine and elsewhere propose a "connection between the epigenome, selective mutability, evolution, and human disease" based on the findings of their study on associations of structural mutability with germline DNA methylation and with non-allelic homologous recombination mediated by low-copy repeats. "Combined evidence from four human sperm methylome maps, human genome evolution, structural polymorphisms in the human population, and previous genomic and disease studies consistently points to a strong association of germline hypomethylation and genomic instability," the Baylor-led team writes.
'Rapid, Inexpensive' CYP2C19 Test of 'Utmost Importance' for Plavix Use
A "rapid and inexpensive" test for CYP2C19 "is of the utmost importance" if physicians are to identify patients who are at "excess risk" of developing cardiovascular events and death while taking the anticoagulant Plavix.
"CYP2C19 genotyping is currently available through a number of laboratories, but you usually have to wait several days to get the result," according to Gilles Montalescot, a researcher at Hôpital Pitié-Salpêtrière in Paris who co-authored a meta-analysis that arrived at the results.
"A quasi-immediate test will be required in the near future if we want to integrate such information in a viable therapeutic algorithm," he added. "A rapid and low-cost test that provides the genetic profile as fast as we get a troponin level will allow genotype-guided antiplatelet therapy."
Echoing other studies, Montalescot's meta-analysis showed that patients who carry the CYP2C19 loss-of-function gene variant "appear to have an excess risk of cardiovascular events and mortality" while taking the blood thinner, which is marketed by Bristol-Myers Squibb and French drug maker Sanofi-Aventis.
The study appears in the July 6 Journal of the American College of Cardiology.
According to Montalescot, "we found that CYP2C19*2 carriage is associated with a higher risk of cardiovascular events, of stent thrombosis, and of death in clopidogrel-treated patients. It is thus becoming increasingly more difficult to ignore the potential of genetic testing."
In March the FDA issued a black box warning for Plavix saying that mutations in the CYP2C19 gene render certain patients unable to respond to the drug, which places them at increased risk for heart attack and stroke.
JACC, which published Montalescot's study, issued guidelines on the black box warning last week.
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