Rheumatoid arthritis, gout, abdominal aortic aneurism (AAA) and inflammatory bowel disease (IBD) may all sound like vastly different conditions, but a group of University of Otago researchers have found plenty of common ground.

Dr Tony Merriman, from the Department of Biochemistry, has successfully secured almost $3.5 million over three years from the Health Research Council for a new research programme titled Application of Genetics to the Pathogenesis of Common Chronic Conditions.

This will bring together his own research group's two related projects on rheumatoid arthritis and gout, with Dr Greg Jones' (Medical and Surgical Sciences) research on AAA and Dr Rebecca Roberts' (Pathology, Christchurch) work on IBD.

Merriman says the three of them had been writing individual project applications, but realised their research has a good common theme, so they decided to go for a programme grant.

"There are synergies between the projects. All involve what we call complex diseases - meaning they have environmental and genetic factors - and they all have an inflammatory component."

A good example of the possible synergies involve Merriman's and colleague Dr Jade Hollis-Moffatt's work on gout, and Dr Jones' research into abdominal aortic aneurism. AAA is found in eight per cent of New Zealand men over the age of 60 and necessitates more than 500 surgical repairs each year at a cost of $8-10 million. Jones will be carrying out a genome-wide association scan (GWAS) looking for genes involved in AAA.

"This technology will allow us to look at 1.8 million genetic markers from each individual," he says. "We can then see which of those 1.8 million markers are associated with being in the disease group and compare them with those in the control group."

Over a period of several years Otago researchers have developed an extensive, disease-free control group of 600 so-called "healthy elderly" who are unaffected by AAA, rheumatoid arthritis or IBD. All the projects in the programme will be able to tap into this unique control group.

Merriman's own team will be looking at several genes thought to be involved in gout, one of the more common forms of arthritis, which affects 10-15 per cent of Māori and Pacific Islands men. It is caused by high levels of uric acid, which then crystallise in the joints and produce inflammation.

One of the key candidate genes is GLUT9, a transporter that grabs uric acid back out of the urine. An overactive copy of the gene makes people more susceptible to gout.

The research team hopes to recruit up to 2,000 people for the study and will be working with the Counties Manukau District Health Board and the Middlemore Māori Gout Action Group.

Merriman will also be carrying out research into the GRIK2 gene, which appears to provide a link between rheumatoid arthritis and schizophrenia. "It's actually a negative association. People with one disease are less likely to get the other," he says. "Getting an insight into why could provide important information on both diseases."

It seems GRIK2 plays a role in both brain development and immune system development so, by characterising its association with each condition, they will be able to learn more.

Merriman says the recent establishment of a $40 million New Zealand Genomics Infrastructure, which will bring together expertise and resources from the University of Otago, Massey University, the University of Auckland and AgResearch, will be vital in examining this gene.

"It is a monster of a gene and more complex than most, which seems to be a characteristic of neurological genes."

Inflammatory bowel disease, the fourth project in the programme, will also make good use of the healthy elderly control group. Principal investigator Roberts says there are two main forms of IBD - ulcerative colitis and Crohn's disease.

There has been an exponential increase in both forms since the 1950s and they now make up vast proportions of outpatients in the gastroenterology clinics. Both usually arise when people are in their 20s and 30s and are lifelong chronic diseases

"Complex diseases like these won't be caused by just a gene or genes. They interact with other factors such as gut microbes and environmental factors."

Roberts says they have more than 1,200 IBD patients, thanks to their clinical team headed by Dr Richard Gearry and Associate Professor Murray Barclay from the Department of Gastroenterology (Christchurch).

They will use a genome-wide association study to screen patients' genetic profiles and identify regions of DNA which may alter susceptibility to IBD, she says.

"What is coming out in the literature is that the genes identified so far only explain about 20 per cent of the genetic susceptibility of IBD."

Merriman says the programme will take the pressure off all three research groups in terms of continual grant application writing.

"We can now sit down and plan an ongoing programme. It has been quite a boost."