Every year, about half of the more than one million people in the United States who have a heart attack survive. But because the first heart attack increases their risk for another one, these people must make major adjustments in their lives to keep their hearts healthy in the future.

In addition to adopting a healthy diet, quitting smoking and losing weight, most people who’ve had a heart attack take medications to help further reduce their risk. Clopidogrel — sold under the trade names Plavix, Iscover, Clopilet and Ceruvin — is a drug commonly prescribed (often in combination with aspirin) to help prevent platelets in the blood from forming clots that can block blood flow to the heart.

Clopidogrel is converted into its active form once it is inside the body. But some people carry genetic variants that reduce the activity of an enzyme central to this conversion process, which in turn reduces the amount of active clopidogrel in the bloodstream and the effectiveness of the drug in preventing clots. Three reports published online this week – two in the New England Journal of Medicine and one in The Lancet – show that these genetic variants can increase the chances that a patient will suffer a second major cardiovascular event.

Jessica Mega and co-workers from Brigham and Women’s Hospital and Harvard Medical School in Boston tracked 1,477 subjects who had had unstable angina or a heart attack and were taking clopidogrel.

Their results, published in NEJM, showed that those people who carried one or more copies of a function-reducing variation in the CYP2C19 gene that (referred to as *2, *3, *4 and *5) had 1.53 times the risk of having a heart attack, stroke or dying from cardiovascular causes compared to non-carriers. The risk of a stent-blocking clot (in those patients who had stents implanted during angioplasty to keep their arteries open) was increased three-fold.

The second NEJM report, from researchers at several Paris hospitals led by Tabassome Simon, showed that in a group of 2,208 heart attack patients taking clopidogrel, carrying two CYP2C19 variants (any combination of *2, *3, *4, or *5) led to a 1.98 times increased risk of heart attack, stroke or death from any cause. Among the 1,535 patients who underwent angioplasty while in the hospital, having two function-reducing CYP2C19 variants increased the risk of cardiovascular events by 3.58 times.

Unlike the study from Mega et al, Simon and colleagues did not see an increased risk in those people with only one copy of a CYP2C19 function-reducing variant.

Finally, Jean-Philippe Collet and colleagues (also from Paris, France) followed the outcomes for 259 young (< 45 years old) heart attack patients taking clopidogrel. Their results, published in The Lancet, showed that having one or two copies of the CYP2C19*2 variant increased the risk of a second heart attack by 4.54 times. The risk of a stent-blocking clot increased 6.02 times.

Collet et al did not investigate the other CYP2C19 variants included in the other reports.

(23andMe customers can check whether they carry any of the CYP2C19 variants mentioned in these reports, except for CYP2C19*5, using the Browse Raw Data feature. See the table at the end of this post for more information.)

Although the magnitude of the effect of CYP2C19 variants was different in each report, all three did show that versions of the CYP2C19 gene that reduce its ability to activate clopidogrel also increased the risk of a second cardiovascular event in those patients who have already suffered one. Based on these results, both Simon et al and Collet et al suggest that genotyping patients might be a good alternative to the current practice of monitoring their platelet response to clopidogrel.

But in a commentary accompanying the report in The Lancet, Dr. Robert Storey of the Cardiovascular Research Unit at the University of Sheffield School of Medicine, UK, argues that testing platelet function in patients is faster than genotyping, and has the added benefit of finding patients who are not responding to clopidogrel due to factors other than CYP2C19 variants, such as age, diabetes, renal failure and cardiac failure.

“Genotyping of patients with acute coronary syndrome is not necessarily the appropriate solution without further work to validate such an approach,” he writes.

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Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss in the western world among people over 60. The two forms of the disease – wet and dry – both cause vision loss by destroying cells in the central portion of the retina.

In the last few years, progress in understanding AMD has been made thanks in part to the discovery of several common genetic variants, or SNPs, that together explain a large part of the risk for the disease. Several of these recently discovered AMD SNP associations have pointed to a role for the immune system in the disease.

A new study published online Monday in The Lancet yet again links the immune system to AMD. As is the case for several of the previously found SNPs, the variant found in this study is in a gene involved in the complement pathway, an arm of the immune system that facilitates the elimination of both pathogens and cellular debris.

Many years ago some researchers suspected that the complement system might be involved in AMD. Proteins from this pathway were found in drusen, the small crystalline deposits that build up in the eyes of people with AMD. But it was not until genetic studies started to show a link between AMD and complement genes that other scientists began to sit up and take notice.

In two separate samples — one British with 479 AMD patients and 479 controls, the other from the U.S. with 248 cases and 252 controls — Ennis et al found that the odds of developing AMD were reduced for every A T a person had at SNP rs2511989. Those with one A T had 0.68 times the odds of people with the GG CC genotype, and people with two As Ts had 0.44 times the odds.

(23andMe customers can check their data for rs2511989 using the Browse Raw Data feature. Note: The original post talked about As and Gs.  But our Browse Raw Data actually gives the data in terms of Ts and Cs.  Two different ways of looking at the same thing!  Sorry for the confusion!)

SNP rs2511989 is in the SERPING1 gene, which encodes a protein that regulates the complement pathway.

“Our findings add to the growing understanding of the genetics of age-related macular degeneration, which should ultimately lead to novel treatments for this common and devastating disease,” the authors write.

In an accompanying comment in The Lancet, Caroline Klaver and Arthur Bergen, two scientists not associated with the research, said the results of Ennis et al need to be replicated in large, independent samples before SERPING1 will be established as a true risk factor for AMD. They also suggest that the researchers may find other SNPs within the gene that are even more tightly linked to AMD.

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