AN INTERNATIONAL study led by researchers in Glasgow has discovered two genes which appear to influence whether heavy drinkers go on to develop alcohol-related liver disease.
The study, based on DNA samples from nearly 40,000 patients from the UK and Europe, identified one gene associated with a lower risk of developing cirrhosis, and another which corresponded to an increased predisposition to the disease.
Until now, little has been known about any genetic basis for the condition.
There is no cure for cirrhosis but researchers believe their findings could pave the way to new treatments and earlier diagnosis.
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Dr Hamish Innes, an epidemiologist and biostatistician at Glasgow Caledonian University who led the research with colleagues in Germany, said: “We wanted to better understand why some heavy drinkers develop alcohol-related cirrhosis but others don’t.
"For a long time we’ve known that genetic factors play a role, but the specific genes involved were a total mystery."
Cirrhosis is known as the silent killer because symptoms are not apparent until the liver is already severely damaged.
The Scottish Health Survey shows that 24 per cent of people in Scotland are drinking at hazardous or harmful levels, putting themselves at risk of cirrhosis.
Although it has fallen significantly in the past 20 years, Scotland still has the highest rate of deaths caused directly by alcohol in the UK. Three-quarters of these "alcohol-specific" deaths in 2018 were caused by alcoholic liver disease.
Genetic data for the study was gathered using samples stored at the UK Biobank from 35,839 heavy drinkers, plus more than 3000 patients attending specialist liver clinics across Europe.
The large sample enabled scientists to drill down into DNA to spot any genetic variants which recurred at a statistically significant level in patients with cirrhosis.
Dr Innes added: “The reason why it has been so difficult to identify these hidden genes is that you need huge numbers in your analysis. You just can’t just do it with a small sample size.
"The UK Biobank is a great starting point for trying to find these hidden genes because there are half a million middle-aged people from the UK which is the demographic most commonly affected by cirrhosis.
“From the half a million there were almost 36,000 heavy drinkers. That’s a good number of people and we had six million genetic factors for these participants, so we looked at the association of all those variants and found about 50 gene suspects.
"We then tested these 50 gene markers in patients who had alcohol-related cirrhosis across Europe, including in Germany and Switzerland."
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After adjusting for age, sex, body mass index (BMI), and Type 2 diabetes, the researchers were able to pinpoint two significant variants.
One, in the MARC1 gene on chromosome one, was associated with a 76% lower risk of alcohol-related cirrhosis, and the second in the HNRNPUL1 gene on chromosome 19 which corresponded to a 130% increased risk of the disease.
"These genes will now be explored by other scientists in the field and ourselves and will hopefully provide new biological clues that could herald breakthrough treatments and better prevention," said Dr Innes.
The findings of the two-year study have been published in the Gastroenterology journal.
The research was jointly led by Dr Stephan Buch from University Hospital Dresden in Germany, and involved experts from 20 different institutions across Europe.
Dr Buch said: “We were able to show that we can distinguish those patients who are at high risk and those that are at much lower risk purely on the basis of their genetic make-up.
"The findings could potentially lead to new treatments and help clinicians differentiate between high and low risk patients.”
Professor Felix Stickel, a German hepatologist and expert in liver disease, added: “The gene variants identified in this study provide novel insight into pathophysiology and possible treatment clues for a disease for which no liver-focused treatment exists.”
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