Centre for Genomic & Experimental Medicine
Centre for Genomic & Experimental Medicine

CGEM scientists identify key gene in bowel disease

April 2017: A key gene that helps explain an underlying cause of incurable bowel disorders has been identified by scientists.

Crohn’s and Colitis UK Awards 2016

Inflammatory Bowel Disease, or IBD, includes Crohn's Disease and Ulcerative Colitis and affects around 300,000 people in the UK. The causes of these debilitating disorders are unknown and there is currently no cure.

The study, led by CGEM researchers Dr Gwo Tzer Ho and Professor Jack Satsangi shows that blocking a single gene harms vital parts of the cell and leads to bowel disease, while targeting these vital cell parts with drugs can reverse damage.

The findings help us understand the cause of these lifelong conditions and could lead to new treatments, scientists say.

IBD has a serious impact on quality of life, with 6,000 new cases diagnosed per year in the UK. We have shown that MDR1 and mitochondrial function are important jigsaw pieces in the complex causes of the disease.

Dr Gwo-Tzer Ho, CGEM

The researchers analysed genetic data from 90,000 people, 40,000 of whom had IBD, to identify the gene – known as MDR1 – which is involved in removing damaging substances from intestinal cells of the gut. The research team showed that MDR1 function was lower in colonic biopsies from people with inflamed IBD compared with those without inflammation.

To demonstrate how MDR1 dysfunction leads to bowel damage, the scientists showed that mice lacking MDR1 had faulty mitochondria – parts of the cell often referred to as ‘batteries’ - which play a vital role in energy generation and cell health. This mitochondrial dysfunction resulted in colitis – inflammation in the inner lining of the bowel that is a defining feature of IBD. Scientists further implicated the role of mitochondria by linking IBD to a large number of genes involved in regulating these cell batteries.

The study also showed that a drug called Mitoquinone – which protects the mitochondria against toxins – can reduce colitis and promote bowel recovery in the mice lacking MDR1, which scientists say is a significant step forward.

The research – carried out in collaboration with researchers at the University of Bristol and in the USA and Japan – was funded by the Medical Research Council and Crohn’s and Colitis UK. It is published in the journal Mucosal Immunology.

Related Links

Journal article

Dr Gwo Tzer Ho's BBC Radio interview with Mhairi Stuart

Dr Gwo Tzer Ho

Professor Jack Satsangi

Crohn's and Colitis UK

Medical Research Council