Gout

Gout is caused by elevated levels of a chemical called uric acid in the blood. In New Zealand gout affects 10-15% of Maori and Pacific Island men, and 1-2% of European men. About four times as many men as women get gout. When levels of uric acid get too high, crystals are formed in the joints, with very painful attacks of gout resulting from the immune system recognising the crystals as 'foreign', and inflaming the joint. The primary reason for people having high uric acid levels is an inherited tendency to excrete less uric acid through the kidneys. However, excess fructose in the diet, and foods rich in purine precursors of uric acid also raise uric acid levels. Uric acid levels in the blood can be reduced using the common drug allopurinol which targets production of uric acid in the blood.Uricosuric drugs such as probenecid and benzbromarone can be more effective as they increase removal of uric acid through the kidneys, targeting the primary reason for gout in most people.

Our research: The 'Genetics of Gout in Aotearoa' project

We are taking a genetic approach to the understanding of the biological causes of gout. We are comparing the frequency of genetic variants that we think cause gout between people with and without gout. This is being done mainly in Auckland and in collaboration with Ngati Porou Hauora. To do this research requires people with and without gout to donate DNA samples. If you live in Auckland or the East Coast and wish to take part, please contact us (tony.merriman@otago.ac.nz). To those people who have already generously donated samples for the study, we thank you.

Our research results

Our first results show that a specific genetic variant within a gene called SLC2A9 approximately doubles your risk of gout if you are of European ancestry. However, if you are of Maori or Pacific Island ancestry, this variant increases your chance of gout by more than five times. Interestingly, this gene is targeted by the drug benzbromarone, which is not easily available to doctors in New Zealand. Our research results are helping the New Zealand Rheumatology Association and the Middlemore Maaori Gout Action Group to work with PHARMAC so as benzbromarone can be made more widely available. Our second results, on the ABCG2 gene, show that the interited component of gout differs between populations, even within people of Polynesian ancestry. At ABCG2 it causes gout in Pacific and European people, but not Maori.

Fructose and gout

Recent studies in North America have shown that soft drinks sweetened with High Fructose Corn Syrup, but not artificially sweetened soft drinks, are associated with higher levels of uric acid and gout. This association was also seen with fruit juice, and also with the eating of larger amounts of fruit. Fructose is also a component of refined sugar (sucrose = one part fructose and one part glucose). Unlike glucose, the metabolism of fructose is not regulated, with one side-effect being the uncontrolled production of uric acid in the blood, thus increasing the chances of gout. In New Zealand, for example, gout was rare in Maori people 100 years ago. Now it is very frequent, with a common 'trigger' of gout attacks being seafood. However, Maori ate a lot of seafood traditionally, with very little gout documented. Today we eat about 50 times more sugar and fructose than 100 years ago. Increasing fructose consumption is part of the reason why gout is so frequent now. Our advice to people with gout is to drink only water, coffee and tea, and to reduce consumption of fruit. Interestingly, this was recognised over 100 years in ago: in 1893 W. Osler prescribed diets low in fructose as a way to prevent gout. He wrote: "The sugar should be reduced to a minimum. The sweeter fruits should not be taken." Seeherefor information on fructose content of fruit (grapes are the worst).

The Middlemore Maaori Gout Action Group

The Middlemore Maaori Gout Action Group (MGAG) is a group of health professionals hosted by Counties Manukau DHB that is united in improving the lives of those with gout, in particular Maaori. A paper describing the MGAG can be downloaded as a pdf here.

The Middlemore Maaori Gout Action Group has hosted two Hui at Te Manukanuka Marae at Auckland airport, which were aimed towards disseminating knowledge about the causes and management of gout. The Proceedings of the March 13 2009 Hui (Outing Gout I) can be downloaded as a pdf here and the Proceedings of the November 6 2009 Hui (Outing Gout II) can be downloaded as a pdf here. Outing Gout III washeld in collaboration with Ngati Porou Hauora at Pakirikiri Marae in Tokomaru Bay March17/18 2011, proceedings can be downloaded as a pdf here. Outing Gout IV was held in collaboration with Te Runanga O Ngati Whatua at Rawiri Marae in Helensville Oct 31/Nov 1 2012. Programme and presenter presentations from Outing Gout IV are downloadable following:

Programme

Tony Merriman – Causes of gout

Tony Merriman – Hospitalization patterns

Nicola Dalbeth - Gout prevalence in New Zealand

Lisa Te Morenga - Sugary drinks, fruit and uric acid

Nicola Dalbeth – Erosions and imaging in gout

Sarah Stewart - Footwear and gout

Tony Merriman – The genetics of gout in Tairawhiti

Nicola Dalbeth – Best practice in management of gout

Janak de Zoysa - Kidney disease, causes and management

Bruce Arroll - Dr info primary care audit and blister packs

Karen Lindsay - The barriers to gout treatment in primary care

Tony Merriman – Gout research project in the Ngati Whatua rohe

 

Our gout publications

Robinson P, Merriman TR, Herbison P, Highton J (2013) Hospital admissions associated with gout in New Zealand and England 1998-2011. Rheumatology 52:118-126. PubMed

Hollis-Moffatt JE, Phipps-Green AJ, Chapman B, Jones GT, van Rij A, Gow PJ, Harrison AA, Highton J, Jones PB, Montgomery GW, Stamp LK, Dalbeth N, Merriman TR (2012) The renal urate transporter SLC17A1 locus: confirmation of association with gout Arthr Res Ther 14:R92 PubMed 

Hollis-Moffatt JE, Phipps-Green AJ, Merriman ME, Topless R, Gow PJ, Harrison AA, Highton J, Jones PBB, Stamp LK, Dalbeth N, Merriman TR (2011) The SLC2A9 non-synonymous Arg265His variant and gout; evidence for a population-specific effect on severity. Arthr Res Ther 13:R85 PubMed

Hsu A, Dalbeth N, Gow P, Harrison A, Highton J, Jones PB, Stamp LK, Merriman TR (2012) Comment on: Genetic association of polymorphism with gout Rheumatology 51:1129-30. PubMed

Robinson PC, Taylor WJ, Merriman TR (2012) A Systematic Review of the Prevalence of Gout and Hyperuricemia in Australia. Internal Med J Apr 4. [Epub ahead of print] PubMed

Merriman TR (2011) Population heterogeneity in the genetic control of serum urate. Semin Nephrol 31:420-5. PubMed

Merriman TR, Dalbeth N (2011) The genetic basis of hyperuricaemia and gout. Joint Bone Spine. 78:35-40PubMed

Phipps-Green AJ, Hollis-Moffatt JE, Dalbeth N, Merriman ME, Topless R, Gow PJ, Harrison AA, Highton J, Jones PBB, Stamp LK, Merriman TR (2010) A strong role for the ABCG2 gene in susceptibility to gout in New Zealand Pacific Island and Caucasian, but not Maori, case and control sample sets. Hum Mol Genet 19:4813-9. PubMed 

Dalbeth N, Merriman TR (2009) Crystal ball gazing; new therapeutic targets for hyperuricaemia and gout. Rheumatology 48:222-6.PubMed 

Hollis-Moffatt JE, Xu X, Dalbeth N, Merriman ME, Topless R, Waddell C, Gow PJ, Harrison AA, Highton J, Jones PBB, O'Donnell JL, Stamp LK, Merriman TR (2009) A role for the urate transporter SLC2A9 gene in susceptibility to gout in New Zealand Maori, Pacific Island and Caucasian case-control sample sets. Arthritis and Rheumatism 60:3485-92. PubMed

Winnard D, Kake T, Gow P, Barratt-Boyes C, Wall L, Hall, D.-A., Merriman T, Mason H, Wilson G, Dalbeth N (2008) Debunking the myths to provide 21st century management of gout. NZ Med J 121:1274PubMed