With genetic testing gaining traction across the world, the American Heart Association (AHA) issued a scientific statement on what healthcare professionals and individuals can do when a gene associated with cardiovascular disease (CVD) is incidentally detected while undergoing genetic testing for non-cardiac reasons, say cancer. Now that heart attacks are being increasingly reported among younger people, should there be greater emphasis on genetic testing?
Titled ‘Interpreting Incidentally Identified Variants in Genes Associated with Heritable Cardiovascular Disease’, published on March 27, the paper “suggests next steps to determine whether a variant truly carries a health risk and suggests appropriate follow-up actions to care for people with variants deemed higher risk for CVD.” According to AHA, variants associated with CVD risk are often found “incidentally” when people undergo genetic testing for non-cardiac reasons, including screening or diagnosis of other diseases.
How are gene variants interpreted and what do they mean in the Indian context?
Ahmedabad-based interventional cardiologist and Director, Cardiology Services, Apollo CVHF Heart Institute, Dr Sameer Dani says, “There is much stronger association with prediction of disease from gene variants as far as dyslipidemias, that is cholesterol issues, cardiomyopathies, certain congenital heart diseases and certain arrhythmias are concerned. But when we talk about heart attacks or Coronary Artery Disease (CAD), world over, the association with gene variants is not so strong as of now. So basically, with genetic testing, we can predict that this child will develop dyslipidemia or cardiomyopathy or arrhythmia, but when it comes to heart attacks, the factors are very many and that is why prediction through gene variants is more difficult.”
Dr Dani says that data on genetic association with CVDs are less, but multiple studies are on, especially in the southern part of India and in the overall Asia-Pacific population, where Indians are also represented. “In heart attacks, there is one gene locus that has been identified as being strongly correlated — chromosome 9p21 – among all populations. In India specifically, some studies have found that there are certain genetic loci, which are specifically important for the Indian population and one of them is Lipoprotein (a), a gene with a significant association of CAD. This gene has been found to have higher expression in the Indian population compared to the Caucasian population. In one of the studies, rs10455872 of LP(a) gene showed a profound risk for CAD in the population from Hyderabad. We have a lot of data like this but we are trying to understand what it means and how to apply that,” says Dr Dani.
Should we recommend a test considering that the CVD risk is spiralling in young people?
Dr Dani says, “Ideally, yes, because it seems genetic testing can tell us who is predisposed to such premature heart attack risks. But it is also always genetics plus environment. So, if you have bad genes but a good lifestyle and environment and can take care of other risk factors, then you can mitigate the influence of bad genes to some extent. Genetic testing can help us identify those at higher risk and push them harder towards a healthy lifestyle from childhood or young age. So, it has very exciting prospects that way. The field is still evolving and it is going to take some time before we can predict with certainty as to who will get a heart attack and who will not. As such the data is very small all over the world on gene variants associated with CVD, but in India the data is even less. There are three processes — you gather the data, you assimilate that data so that you understand how to apply the data and then you implement that knowledge in treatment protocol or prevention strategy of the disease. Right now, we are in the data collection stage.”
What remains the challenge with genetic testing being commonplace in India?
Cost and ethical concerns are two challenges that Dr Dani highlights. “To do a whole genome sequencing is expensive, it can cost more than one lakh rupees although specific gene sequencing costs less than that (with genetic testing not covered under health insurance at present). There are also certain ethical problems. So, once you know this disease is likely, unless the association with the gene variant is very strong and precise, telling the patient about it may create unnecessary anxiety. Sometimes wrong actions may follow. And if there is a strong association of CVD with a particular gene variant and we don’t inform the patient, the patient may suffer adverse consequences. Usually, we would rather address the lifestyle factors in a patient rather than telling the patient that they have a particular gene that may predispose them to CVD because right now there is not a lot of data to be sure of the same,” says he.
But in the US informing patients about incidental variants while getting a genetic test for some other disease is very important especially if there’s research showing the particular gene is predictive of CVD. “If they are not informed, the healthcare professionals can be held legally liable. That’s why pre-test genetic counselling becomes important where they seek consent from the patient if they want to be informed of incidental genes found. So, for example, if a patient is to be gene tested for say, cancer genes and incidentally heart attack gene variants are also detected, the doctors ask the patient if they would want to be informed about the latter,” says Dr Dani.
