Could genetic testing kits help to diagnose our “air health” in the future?
In 2013, Ella Kissi-Debrah died of a fatal asthma attack. The nine-year-old, who lived near the South Circular Road in Lewisham, south-east London, had been suffering from poor respiratory health for 28 months, and was admitted to hospital 28 times. An inquest into her death found that Ella had died from acute respiratory failure and severe asthma.
But in 2018, as the BBC writes: “[a recent] report said it was likely unlawful levels of pollution, which were detected at a monitoring station one mile from Ella’s home, contributed to her fatal asthma attack”.
As a result Judge Mark Lucraft QC, quashed the 2014 inquest and said: “In our judgment, the discovery of new evidence makes it necessary in the interests of justice that a fresh inquest be held.” If high pollution levels are deemed to have played a role in her death, Ella may become the first person in the UK for whom air pollution is listed as the cause of death.
For those studying the health impacts of air quality, much of the focus is still on better understanding the impact pollution has on our bodies. But what if we could say that some people had certain genetic traits or conditions that might make them more susceptible to air pollution?
Genetic testing has been in use for decades, and can today be used to diagnose or predict more than 2000 medical conditions — including cystic fibrosis, Down’s syndrome, Huntington’s disease, and certain types of cancer.
Since 2003, thanks to the Human Genome Project, we’ve had a complete and accurate sequence of the three billion DNA base pairs that make up the human genome, and understanding how our individual genetic codes work is an area of scientific discovery that’s fascinating to researchers, patients and consumers alike.
As the growing market for genetic tests like AncestryDNA and 23andMe demonstrates, we all want to know more about who we are. As researchers continue to build up the base of knowledge about exactly how our genes interact with our environment, this holds exciting possibilities for personalised medicine.
But what could genetic testing tell us about the complex issue of air pollution and its potential impacts on our health? Currently, “there’s not been a huge amount of study in the genetics of air pollution per se,” says John Holloway, Professor of Allergy and Respiratory Genetics at the University of Southampton.
But, he adds, “where people have looked, they’ve identified genetic factors that you can put into two classes: those that mean we’re better able to deal with or detoxify exposures, and those that mean we make a different type of response once we’ve been exposed.”
From this existing research, Professor Holloway explains, “it’s clear that there’s a range of different genetic effects, and some people will respond differently to the same level of exposure — so some people are genetically more susceptible to experiencing the adverse effects of air pollution.”
Where this gets complicated, he explains, is that: “of course, air pollution is a complex mix of different chemicals and particles, so you’ve got to tease apart precisely what an individual will be susceptible to.”
If you take air pollution from diesel, for example, you need to work out if an individual is responding to the particles within it, or the heavy metals, or the organic compounds. “All of those responses are going to vary from individual to individual,” Professor Holloway says. “Equally, for those who are exposed, some will be more likely than others to develop disease as a result.”
In other words, adverse health effects from air pollution are caused by a combination of different factors working together. While some people may be genetically more predisposed to asthma, for example, they still require the right environmental trigger to cause the disease to develop.
Another complexity presented by air pollution is the range of adverse health impacts it’s associated with. “As a geneticist, one of the things you think about is how the effects of exposure to, say, ozone or particulate matter, elicits a number of different responses, so it’s not just one response you’d be interested in,” explains Steven Kleeberger, Director of the Environmental Genetics Group at the National Institute of Environmental Health Sciences in the US.
“Ozone, for instance, causes inflammation, yet also causes effects on the cardiovascular systems. Each of these phenotypes (an observable physical property) is likely controlled by a separate set of genes, so you’re looking at multiple genes for multiple phenotypes,” he explains.
Compare this to genetic testing for a BRCA gene mutation, for example, which increases the risk of breast and ovarian cancer. BRCA testing involves looking at one or two genes (BRCA1 and BRCA2) to identify someone’s predisposition to one or two responses (breast and/or ovarian cancer).
Genetic testing for air pollution would involve looking at a whole range of genes to identify a predisposition to a whole range of responses, which could be triggered by a whole range of different pollutants. It’s no wonder, as Dr Kleeberger says, that there are still more clinical studies and more epidemiology research needed in this area.
Despite this, he says, “I think it’s absolutely probably that, in the future, genetic testing could be used to determine someone’s susceptibility to the effects of air pollution. Maybe in the next decade.”
Outlining how this could work, Dr Kleeberger explains: “Ideally what we would have is a diagnostic tool, or a panel of genes that would give you information on all of these different phenotypes or responses. Then a clinician could use this as a means of identifying people who are susceptible, and come up with a plan.”
In effect, he adds, this could be used to offer tailored advice to individuals who are otherwise healthy but, because of their genetic background, could be susceptible to the effects of air pollution. “What we’re talking about is really personalised medicine. If people can be identified as being susceptible, ideally you could act early to extend that person’s lifetime.”
One example might be using drugs like an anti-TNF therapy to reduce the effects of the gene TNF (tumour necrosis factor), which is associated with inflammatory conditions like asthma.
Like Dr Kleeberger, Professor Holloway believes genetic testing for air pollution susceptibility will be conceptually possible in the next decade or so. “The technology enables us to sequence someone’s genome now. Once you know all someone’s genetic variants, you need to match that to knowledge about how it relates to risks from different exposures,” he explains.
“On the air pollution side, we haven’t got as much of that because it’s often very difficult to assess an individual’s exposure. Theoretically, as we understand more and more about the genetic factors that drive responses to air pollution, it would be possible in the future to classify people like that.”
At an individual level though, Professor Holloway believes the effects are likely to be much smaller. “Like any common disease — whether that’s heart disease or asthma — a response to air pollution is going to be the effect of hundreds of different genetic variants within each individual’s genome,” he explains.
“It may be possible to identify those that are at higher risk and those that are at lower risk. But whether that would happen routinely in a healthcare setting, and whether it would affect behaviours, I don’t know. We can tell people they’re at risk of heart disease now, but convincing them to change their lifestyles is more difficult,” Professor Holloway adds.
Beyond personalised medicine, he believes genetic testing around air pollution susceptibility could have broader implications for public health. “I think the most likely impact in public health terms will be to actually identify the level of pollution that will trigger disease in a susceptible individual,” he says.
“At the moment, when governments try to work out what is a safe level of exposure, of course they’re doing that based on the average population. Within that, some people will be more susceptible than others,” Professor Holloway explains. “If we can identify those susceptible individuals, and know what level of air pollution exposure is safe for them, that could help inform policy about what we should really be setting as a safe limit.”
Words: Sarah Graham, freelance science journalist
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