How a £140 DNA test could prevent as many as 100,000 strokes a year

Sarah-Jane Kirkaldy never expected the treatment for her illness would be worse than the disease itself – or that a simple test could have saved her from its life-threatening side effects.

The 47-year-old IT manager from Wokingham was diagnosed with the painful bowel condition Crohn’s disease in 2007, and struggled to find any relief with standard medication. Then, in 2009, her gastroenterologist suggested a daily dose of the immune-suppressing drug azathioprine to control inflammation in her guts.

‘A couple of weeks after I started taking it I was in my car, on the motorway, and started to feel drunk,’ says Sarah-Jane. ‘I felt dreadful, as if I was really spaced out and bleary-eyed. I knew something wasn’t right, but put it down to being tired.’

The simple test, which involves taking either a blood sample or a swab from the mouth, tells doctors if the drug will work and whether the patient will develop side effects, based on their genes

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Roughly one million prescriptions for azathioprine are written every year, but in about one in ten patients it causes a potentially fatal side effect when the drug kills off the body’s infection-fighting white blood cells and blood pressure falls dangerously low, known as septic shock.

The next day, Sarah-Jane had a call from her GP and was told to stop taking the pills. She says: ‘The blood tests I’d been having since starting treatment showed my white blood cell count had plummeted and I was in desperate need of a blood transfusion.’

She was admitted to the Royal Berkshire Hospital, where she stayed for two weeks and received three blood transfusions.

Two weeks after she was discharged, Sarah-Jane woke one morning to find her skin covered in dark dots. She says: ‘I had rapid heart palpitations, a rocketing temperature and the spaced-out feeling was back again. I called the doctor, who ordered me to go straight to A&E.’

She had developed pneumonia and sepsis – the early stage of sceptic shock where patches of skin look blue and bruised – and her white blood cells had dropped to dangerously low levels. She adds: ‘My mother gasped in horror when she saw a flash of my skin through the hospital gown – I was purple all over.’

Sarah-Jane spent two days in intensive care and a further two weeks on a ward until transfusions eventually stabilised her condition.

Last year Sarah-Jane took part in a trial that confirmed she was vulnerable to terrible side effects from azathioprine.

Dr Tariq Ahmad, a consultant gastroenterologist at the Royal Devon and Exeter NHS Foundation Trust, enrolled her in a study aiming to spot genetic vulnerability to side effects from drugs. ‘He explained there was a fault in my DNA that meant my body couldn’t process the drug,’ says Sarah-Jane. ‘If a test [to find the fault] was available to everyone before they’re given the drug, it would be fantastic.’

Now experts are calling for exactly this. In a report published by the British Pharmacological Society and the Royal College of Physicians, doctors from 26 medical specialities called for DNA tests to be available to every patient before they take a high-risk drug.

Scientists can examine a patient's DNA to see if they are likely to suffer an adverse reaction to common treatments

Scientists can examine a patient’s DNA to see if they are likely to suffer an adverse reaction to common treatments

The simple test, which involves taking either a blood sample or a swab from the mouth, tells doctors if the drug will work and whether the patient will develop side effects, based on their genes.

Professor Sir Munir Pirmohamed, NHS chair of pharmacogenetics at the University of Liverpool and co-author of the report, told The Mail on Sunday that the results could be analysed in 20 minutes at a cost of just £140 per patient.

‘Research shows that there are 40 genes that are most crucial in determining how people react to drugs,’ says Prof Pirmohamed. ‘One test allows us to spot the telltale problems with these genes.’

A staggering one million people in England are admitted to hospital each year due to adverse drug reactions, according to experts at the University of Liverpool. But genetic tests to determine risk are available only in specific circumstances.

Since 2020, NHS cancer patients prescribed the chemotherapy drug capecitabine have been offered a test for a genetic variation found in up to eight per cent of people which stops the liver being able to expel excess amounts of the drug.

Patients with HIV who are prescribed the antiretroviral drug abacavir are also screened for a gene that puts them at risk of potentially fatal allergic reaction.

But between 40 and 50 of the most commonly taken medicines, from antibiotics to antidepressants, can have disastrous consequences for someone with a particular genetic make-up, says the report.

The problem can lie with enzymes in the liver that process a medication before it gets to work in the body. Specific genes carry instructions for making these enzymes. But genetic variations mean that some people make too much of the enzyme, others too little.

The result it that some people use up too much of a drug, while others cannot process it at all.

Experts say many of these people have potentially risky variations in genes CYP2D6 and CYP2C19, which govern the way the body handles many common medications. Toxic effects of the painkiller codeine have been linked to CYP2D6 – with those with a mutation processing an unusually large amount of the drug, leading to side effects such as dangerously shallow breathing.

Problems with blood-thinning drug clopidogrel are linked to mutations of CYP2D6 and CYP2C19. The medication is given to heart-attack patients, but studies estimate as many as one in five may have the genetic fault that means it has little to no effect.

It is suggested that a test to spot the mutation could prevent roughly 100,000 strokes each year.

Patients with mutations in another gene, called mt-RNR1, who are given the antibiotic gentamicin to treat bacterial infections, for example, can suffer liver damage, hearing loss and balance problems. Routine screening for the genetic fault could avert about 180 cases of deafness every year in the UK alone, according to a report in the British Medical Journal.

Experts say DNA tests may also help patients with genetic resistance to painkillers and those with anxiety and depression – half of whom fail to respond to antidepressants.

Prof Pirmohamed believes his goal – genetic tests for every patient – may become a reality soon. He says: ‘There’s a Bill making its way through the US Congress that is likely to make it law for doctors to offer these tests. We are usually five to ten years behind the US when it comes to implementing technology like this. Why not be proactive for a change, and do it before everyone else?’

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