Immune system link to kidney disease risk, research finds

29 Jun 2016 19:00:00.000

PA 156/16

A gene which forms part of our body’s first line of defence against infection may be associated with an increased risk with a type of kidney disease, research involving academics at The University of Nottingham has discovered.

The work, which is published in the academic journal Science Translational Medicine, found that the difference in the number of copies of the alpha-defensin genes was a major genetic factor in developing the condition IgA nephropathy.

Professor John Armour, Professor of Human Genetics in the University’s School of Life Sciences, said: “The observation that variation in the gene numbers for these alpha-defensin genes is strongly correlated with risk of IgA nephropathy creates an interesting puzzle.

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“The data overwhelmingly support the association, but we still don’t understand what the connection might be between alpha-defensins and molecular events that cause the kidney problems.”

IgA nephropathy, also known as Berger’s Disease, is a condition in which Immunoglobulin A, one of the types of antibody the body produces to fight infection, settles in the kidney causing scarring and inflammation. The condition can lead to high blood pressure, swollen ankles and high levels of cholesterol in the blood and, in the most serious cases, can lead to kidney failure.

It is a relatively rare condition in Europe, but is much more common in China and East Asia, where it is the leading cause of patients needing dialysis because of kidney failure.

Unexpected conclusion

Previous studies have demonstrated that there are genetic factors involved in predisposition to the disease and scientists have been working to map these factors more precisely.

In this latest study, Professor Armour and colleagues at Nottingham have worked in collaboration with teams at the University of Leicester, Sun Yat-sen University in Guangzhou, China, and the Genome Institute of Singapore.

They came to the unexpected conclusion that the strongest genetic factor is the variation in numbers of genes for defence proteins.

People have two copies of most genes in the human genome, one from each parent, but some genes are present in different numbers in different people.

The team looked at genetic variation in more than 1,000 patients with IgA nephropathy, compared with more than 1,000 people without the condition, and found a significant difference in the numbers of alpha-defensin genes between the two groups.

Alpha-defensins are proteins that kill bacteria as part of the innate immune system, our first line of defence against infection.

Although the findings do not immediately suggest new therapies for the disorder, they will improve our chances of identifying those who are most at risk and offer a new line of investigation to understand exactly how the defensin gene copy number variants lead to kidney disease. The team is already undertaking the next stage of research to further develop our knowledge.

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Notes to editors: The University of Nottingham has 43,000 students and is ‘the nearest Britain has to a truly global university, with a “distinct” approach to internationalisation, which rests on those full-scale campuses in China and Malaysia, as well as a large presence in its home city.’ (Times Good University Guide 2016). It is also one of the most popular universities in the UK among graduate employers and was named University of the Year for Graduate Employment in the 2017 The Times and The Sunday Times Good University Guide. It is ranked in the world’s top 75 by the QS World University Rankings 2015/16, and 8th in the UK for research power according to the Research Excellence Framework 2014. It has been voted the world’s greenest campus for four years running, according to Greenmetrics Ranking of World Universities.

Impact: The Nottingham Campaign, its biggest-ever fundraising campaign, is delivering the University’s vision to change lives, tackle global issues and shape the future. More news…

Story credits

More information is available from Professor John Armour in the School of Life Sciences, University of Nottingham on +44 (0)115 823 0308,

Emma Thorne Emma Thorne - Media Relations Manager

Email: Phone: +44 (0)115 951 5793 Location: University Park

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