As part of five-part series on major new Kiwi research projects, science reporter Jamie Morton speaks to an Otago University team exploring a link between metabolic disease and genetic variants in Pacific people.

Higher rates of gout among Pacific people could lie in a genetic predisposition stretching back thousands of years – something that could clear up harsh stigma and improve healthcare.

Otago University researcher Dr Anna Gosling said it had long been recognised that Maori and Pacific people had much greater burdens of certain type of diseases.

This wasn't just a pattern seen here in New Zealand, but for Pacific people generally – and it also couldn't be put down purely to those sedentary jobs and highly-processed foods of modern life.

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Much of the answer might be found in remains of some of the Pacific's first inhabitants – including those earliers settlers of Vanuatu and Aoteoroa – which bear evidence of gout.

Gosling, with fellow Otago researchers Professor Tony Merriman and Professor Lisa Matisoo-Smith, are now trying to understand when, how and why this predisposition to metabolic diseases evolved.

The mystery wasn't one to be solved easily, as factors ranging from natural selection driven by pathogens like malaria, to random "genetic drift" from island to island all might have played a part.

"These evolutionary explanations are important to explore – partly because of the stigma associated with metabolic diseases," Gosling said.

"This stigma hurts people in a number of ways – not only do people with conditions like gout and diabetes often feel a sense of guilt and self-blame, but society as a whole can be quite unkind because of the common perception that these diseases are a result of poor living and unhealthy lifestyles."

Unravelling the predisposition puzzle would hopefully lessen that stigma, she said.

In the project, supported by grants through the Marsden Fund and the Rutherford Foundation, Gosling and colleagues will be working closely with several communities in under-studied parts of the Pacific.

"We have members of our research team who are based in Kiribati, Yap and Guam in Micronesia, and in Papua New Guinea."

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In these locations, the team will recruit local participants and collect health and ancestry information, along with genetic samples that will undergo DNA sequencing.

"This will allow us to look at unique Pacific genomes and identify unique variations which may be contributing to the burden of metabolic disease in the region," she said.

"These DNA sequences will also allow us to apply complex statistical methods to explore whether natural selection may have taken place in the past, and whether genetic variants associated with metabolic traits may have provided a survival advantage in Pacific environments."

They'll also be testing a new model to explore whether malaria could have played an important role in shaping Pacific genomes – particularly around elevated serum urate levels, which are known thought to guard against malaria parasites, but also contribute to gout risk.

Work led by Merriman has already pin-pointed different genetic variants that are associated with gout, which so far have only been found in Polynesian populations.

Further, some of these vary between people in West Polynesia – Samoa, Tonga, Niue and Tokelau – and those in East Polynesia, or New Zealand, the Cook Islands, Tahiti and Hawaii.

"This got us thinking about the historical and evolutionary implications of these variations," said Matisoo-Smith, renowned for her research on the ancient Pacific.

"The fact that we are combining the genetics of metabolic disease with the evolutionary perspective – understanding how metabolic disease might be related to population history, is what is novel."

Earlier anthropological research has also allowed the team to zero in on specific populations in Papua New Guinea and Micronesia, which should allow the team to test a range of possible explanations.

Matisoo-Smith said the link might even be related to the introduction of European diseases – allowing some people with a particular genetic makeup to survive.

"Generally for common diseases with a genetic basis when you see a genetic trait that is maladaptive yet present, there is likely to be an evolutionary explanation," she said.

"What makes someone sick today may be a genetic adaptation that allowed their ancestors to survive in the past."

Merriman points out, that if it could be demonstrated that selection played a part, this could open the door to new insights which would ultimately lead to long-term improvements in the health system.

He added that Pacific people had also long been grossly under-represented in genomics research – just one in 5000 participants in studies internationally came from an Oceanic population.

"If genomics research is not done with Pacific populations, then we run a risk of increasing health disparities that will result from the application of genomics findings in major population groups - but not minority populations."