GCU scientist finds DNA breakthrough in alcohol-related liver disease

International research led by scientists at Glasgow Caledonian University (GCU) has found a new link between DNA and the risk of alcohol-related liver cirrhosis.

Until now, very little was known about the genetic factors that affect the development of alcohol-related cirrhosis. Every day, more than 40 people die from liver disease in the UK, according to the British Liver Trust.

The Scottish Health Survey shows that a quarter of adults (24 per cent) are drinking at hazardous or harmful levels, putting themselves at risk of alcohol-related liver disease. Cirrhosis is known as the silent killer because symptoms are not apparent until the liver suffers significant damage. There is no cure.

This latest ground-breaking research, published in the Gastroenterology Journal, investigated the link between DNA and the risk of cirrhosis and involved 35,839 heavy drinkers from the UK Biobank resource, plus more than 3000 patients attending specialist liver clinics across Europe.

The two-year study identified two new genetic links which make some drinkers more susceptible to cirrhosis. This information could help clinicians identify patients most at risk and possibly lead to the development of new drugs to prevent and treat this condition.

The research was jointly led by Dr Hamish Innes, an epidemiologist and biostatistician at GCU, and Dr Stephan Buch from University Hospital Dresden in Germany, and involved experts from 20 different institutions across Europe.

Senior authors of the paper entitled ‘Genome-wide Association Study for Alcohol-related Cirrhosis Identifies Risk Loci in MARC1 and HNRNPUL1’ are Professor Marsha Morgan, UCL Institute for Liver & Digestive Health UK, Professor Jochen Hampe, University Hospital Dresden, and Professor Felix Stickel from the University Hospital of Zurich in Switzerland.

Dr Innes 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.

“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.

“From here, we identified two new genetic variants in the MARC1 gene on chromosome 1 and the HNRNPUL1 gene on chromosome 19. 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.”

Genetic variations, or variants, are the differences that make each person’s DNA unique.

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 Stickel, who coordinated the scientific consortium, explained: “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.”

The research is a great example of collaborative science involving 20 different institutions from across Europe, not to mention the generosity and altruism of the study participants themselves.

The research paper can be found here.

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