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Gout: HELP
Articles from Dunedin
Based on 64 articles published since 2008
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These are the 64 published articles about Gout that originated from Dunedin during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Editorial PPARGC1B: insight into the expression of the gouty inflammation phenotype: PPARGC1B and gouty inflammation. 2017

Merriman, Tony / Terkeltaub, Robert. ·Department of Biochemistry, University of Otago, Dunedin, New Zealand. · VA San Diego Healthcare System. · Department of Medicine, University of California San Diego, San Diego, CA, USA. ·Rheumatology (Oxford) · Pubmed #28003496.

ABSTRACT: -- No abstract --

2 Editorial Gout in Māori. 2014

Gosling, Anna L / Matisoo-Smith, Elizabeth / Merriman, Tony R. ·Department of Anatomy, University of Otago, 913 Dunedin, 9054 New Zealand. anna.gosling@anatomy.otago.ac.nz. ·Rheumatology (Oxford) · Pubmed #24067884.

ABSTRACT: -- No abstract --

3 Review Expert opinion on emerging urate-lowering therapies. 2018

Stamp, Lisa K / Merriman, Tony R / Singh, Jasvinder A. ·a Department of Medicine , University of Otago , Christchurch , New Zealand. · b Department of Biochemistry , University of Otago , Dunedin , New Zealand. · c Medicine Service , VA Medical Center , Birmingham , AL , USA. · d Department of Medicine at the School of Medicine , University of Alabama at Birmingham , Birmingham , AL. · e Division of Epidemiology at the School of Public Health , University of Alabama at Birmingham , Birmingham , AL , USA. ·Expert Opin Emerg Drugs · Pubmed #30244605.

ABSTRACT: INTRODUCTION: There has been a resurgence in gout therapeutics in the last decade, not only for the management of gout flares, but also for the treatment of hyperuricemia. This editorial summarizes new, emerging therapies for people with gout. Areas covered: We review several new therapies for gout, including those that are focused on lowering serum urate (levotofisopam, ulodesine, verinurad, merbarone, KUX-1151, UR-1102, FYU-981, SEL-212), or treating gout flares (canakinumab, bucillamine) or both (arhalofenate, diacerein). Expert opinion: Among therapies with both urate lowering and anti-inflammatory action, arhalofenate seems promising, but more data are needed. Examining therapies aimed at treating gout flares [anti-inflammatory action], bucillamine has some potential, but more data and Phase III studies are needed, to better understand its efficacy and safety. Among the urate-lowering therapies (ULTs), verinurad seems to be the most promising, while levotofisopam and ulodesine require more data. A uricase-replacement therapy with improved immune reaction (SLE-212) is in a Phase II trial. A number of ULTs including KUX-1151, UR-1102 and FYU-981 are in early development and more will be known once initial data and studies are published.

4 Review An association of smoking with serum urate and gout: A health paradox. 2018

Fanning, Niamh / Merriman, Tony R / Dalbeth, Nicola / Stamp, Lisa K. ·Department of Medicine, University of Otago, Christchurch, PO Box 4345, Christchurch, New Zealand. Electronic address: niamh.fanning@otago.ac.nz. · Department of Biochemistry, University of Otago, Dunedin, New Zealand. · Department of Medicine, University of Auckland, Auckland, New Zealand. · Department of Medicine, University of Otago, Christchurch, PO Box 4345, Christchurch, New Zealand. ·Semin Arthritis Rheum · Pubmed #29398126.

ABSTRACT: BACKGROUND: The potential effect of cigarette smoking on levels of serum urate and risk of gout has been considered by a large number of studies, either as the primary variable of interest or as a covariate. METHODS: Here we systematically review the published evidence relating to the relationship of smoking with serum urate, hyperuricaemia, and gout. RESULTS: Many studies have reported that smoking reduces serum urate, however, the evidence has not been conclusive with other studies pointing to the opposite or no effect. It has also been suggested that smoking reduces the risk of gout, although there is some evidence to contradict this finding. CONCLUSION: A consensus has yet to be reached as to the effect of smoking on serum urate levels and the risk of gout.

5 Review Association between ABCG2 rs2231142 and poor response to allopurinol: replication and meta-analysis. 2018

Wallace, Mary C / Roberts, Rebecca L / Nanavati, Payal / Miner, Jeffrey N / Dalbeth, Nicola / Topless, Ruth / Merriman, Tony R / Stamp, Lisa K. ·Department of Surgical Sciences, University of Otago, Dunedin, New Zealand. · Biology Department, Ardea Biosciences, Inc., San Diego, CA, USA. · Department of Medicine, University of Auckland, Auckland, New Zealand. · Department of Biochemistry, University of Otago, Dunedin, New Zealand. · Department of Medicine, University of Otago, Christchurch, New Zealand. ·Rheumatology (Oxford) · Pubmed #29342288.

ABSTRACT: Objective: ABCG2 rs2231142 (Q141K) has been reported to be associated with poor response to allopurinol, while there are conflicting data on the association between the genetically independent ABCG2 rs10011796 variant and allopurinol response. The aim of this study was to replicate the association of ABCG2 rs2231142 and rs10011796 with allopurinol response and perform a meta-analysis. Methods: Participants in the Long-term Allopurinol Safety Study Evaluating Outcomes in Gout Patients (LASSO) (n = 299) were studied. In patients with evidence of adherence to allopurinol therapy (plasma oxypurinol >20 μmol/l), good response was defined as serum urate <6 mg/dl on allopurinol ⩽300 mg/day and poor response as serum urate ⩾ 6 mg/dl despite allopurinol >300 mg/day. Association of rs2231142 and rs10011796 with poor response was tested in logistic regression models that included age, sex, BMI, ethnicity and estimated glomerular filtration rate. Results from the LASSO study and a subset of participants in the Genetics of Gout in Aotearoa New Zealand study (n = 296, including 264 from a previously published report) were combined by meta-analysis. Results: There was evidence for association of rs2231142 with allopurinol response [odds ratio (OR) = 2.35, P = 7.3 × 10-4] but not for rs10011796 (OR = 1.21, P = 0.33) in the LASSO cohort using an adjusted logistic regression model. Meta-analysis provided evidence of a significant association of rs2231142 with allopurinol response (OR = 2.43, P = 6.2 × 10-7), but not rs10011796 (OR = 1.06, P = 0.69). Conclusion: This study has confirmed the significant association of ABCG2 rs2231142 with poor response to allopurinol.

6 Review Genomic Influences on Hyperuricemia and Gout. 2017

Merriman, Tony. ·Department of Biochemistry, University of Otago, 710 Cumberland Street, Dunedin 9054, New Zealand. Electronic address: tony.merriman@otago.ac.nz. ·Rheum Dis Clin North Am · Pubmed #28711141.

ABSTRACT: Genome-wide association studies (GWAS) have identified nearly 30 loci associated with urate concentrations that also influence the subsequent risk of gout. The ABCG2 Q141 K variant is highly likely to be causal and results in internalization of ABCG2, which can be rescued by drugs. Three other GWAS loci contain uric acid transporter genes, which are also highly likely to be causal. However identification of causal genes at other urate loci is challenging. Finally, relatively little is known about the genetic control of progression from hyperuricemia to gout. Only 4 small GWAS have been published for gout.

7 Review The genetics of gout: towards personalised medicine? 2017

Dalbeth, Nicola / Stamp, Lisa K / Merriman, Tony R. ·Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Rd, Grafton, Auckland, 1023, New Zealand. n.dalbeth@auckland.ac.nz. · Department of Medicine, University of Otago, Christchurch, New Zealand. · Department of Biochemistry, University of Otago, Dunedin, New Zealand. ·BMC Med · Pubmed #28566086.

ABSTRACT: Over the last decade, there have been major advances in the understanding of the genetic basis of hyperuricaemia and gout as well as of the pharmacogenetics of urate-lowering therapy. Key findings include the reporting of 28 urate-associated loci, the discovery that ABCG2 plays a central role on extra-renal uric acid excretion, the identification of genes associated with development of gout in the context of hyperuricaemia, recognition that ABCG2 variants influence allopurinol response, and the impact of HLA-B*5801 testing in reducing the prevalence of allopurinol hypersensitivity in high-risk populations. These advances, together with the reducing cost of whole genome sequencing, mean that integrated personalised medicine approaches may soon be possible in clinical practice. Genetic data may inform assessment of disease prognosis in individuals with hyperuricaemia or established gout, personalised lifestyle advice, selection and dosing of urate-lowering therapy, and prevention of serious medication adverse effects. In this article, we summarise the discoveries from genome-wide association studies and discuss the potential for translation of these findings into clinical practice.

8 Review Gout. 2016

Dalbeth, Nicola / Merriman, Tony R / Stamp, Lisa K. ·Department of Medicine, University of Auckland, Auckland, New Zealand. Electronic address: n.dalbeth@auckland.ac.nz. · Department of Biochemistry, University of Otago, Dunedin, New Zealand. · Department of Medicine, University of Otago, Christchurch, New Zealand. ·Lancet · Pubmed #27112094.

ABSTRACT: Gout is a chronic disease of deposition of monosodium urate crystals, which form in the presence of increased urate concentrations. Although environmental factors contribute to hyperuricaemia, renal and gut excretion of urate is central to regulation of serum urate, and genetic factors are important. Activation of the NLRP3 inflammasome and release of interleukin 1β have key roles in initiation of acute gout flares. A "treat to target serum urate" approach is essential for effective gout management; long-term lowering of serum urate to less than 360 μmol/L leads to crystal dissolution and ultimately to suppression of flares. An allopurinol dose-escalation strategy is frequently effective for achieving treatment targets, and several new urate-lowering drugs are also available. Worldwide, rates of initiation and continuation of urate-lowering therapy are very low, and, consequently, achievement of serum urate targets is infrequent. Strategies to improve quality of gout care are needed.

9 Review Pacific Populations, Metabolic Disease and 'Just-So Stories': A Critique of the 'Thrifty Genotype' Hypothesis in Oceania. 2015

Gosling, Anna L / Buckley, Hallie R / Matisoo-Smith, Elizabeth / Merriman, Tony R. ·Department of Biochemistry, University of Otago, Dunedin, New Zealand. · Department of Anatomy, University of Otago, Dunedin, New Zealand. · Allan Wilson Centre for Molecular Ecology and Evolution, University of Otago, Dunedin, New Zealand. ·Ann Hum Genet · Pubmed #26420513.

ABSTRACT: Pacific populations have long been observed to suffer a high burden of metabolic disease, including obesity, type 2 diabetes and gout. The 'Thrifty Genotype' hypothesis has frequently been used to explain this high prevalence of disease. Here, the 'Thrifty Genotype' hypothesis and the evolutionary background of Pacific populations are examined. We question its relevance not only in the Pacific region but more generally. Not only has the hypothesis not been explicitly tested, but most archaeological and anthropological data from the Pacific fundamentally do not support its application.

10 Review An update on the genetic architecture of hyperuricemia and gout. 2015

Merriman, Tony R. ·Department of Biochemistry, University of Otago, Box 56, Dunedin, 9054, New Zealand. tony.merriman@otago.ac.nz. ·Arthritis Res Ther · Pubmed #25889045.

ABSTRACT: Genome-wide association studies that scan the genome for common genetic variants associated with phenotype have greatly advanced medical knowledge. Hyperuricemia is no exception, with 28 loci identified. However, genetic control of pathways determining gout in the presence of hyperuricemia is still poorly understood. Two important pathways determining hyperuricemia have been confirmed (renal and gut excretion of uric acid with glycolysis now firmly implicated). Major urate loci are SLC2A9 and ABCG2. Recent studies show that SLC2A9 is involved in renal and gut excretion of uric acid and is implicated in antioxidant defense. Although etiological variants at SLC2A9 are yet to be identified, it is clear that considerable genetic complexity exists at the SLC2A9 locus, with multiple statistically independent genetic variants and local epistatic interactions. The positions of implicated genetic variants within or near chromatin regions involved in transcriptional control suggest that this mechanism (rather than structural changes in SLC2A9) is important in regulating the activity of SLC2A9. ABCG2 is involved primarily in extra-renal uric acid under-excretion with the etiological variant influencing expression. At the other 26 loci, probable causal genes can be identified at three (PDZK1, SLC22A11, and INHBB) with strong candidates at a further 10 loci. Confirmation of the causal gene will require a combination of re-sequencing, trans-ancestral mapping, and correlation of genetic association data with expression data. As expected, the urate loci associate with gout, although inconsistent effect sizes for gout require investigation. Finally, there has been no genome-wide association study using clinically ascertained cases to investigate the causes of gout in the presence of hyperuricemia. In such a study, use of asymptomatic hyperurcemic controls would be expected to increase the ability to detect genetic associations with gout.

11 Review Pharmacogenetic considerations in the treatment of gout. 2015

Roberts, Rebecca L / Stamp, Lisa K. ·Department of Surgical Sciences, Dunedin School of Medicine, Dunedin, New Zealand. ·Pharmacogenomics · Pubmed #25876828.

ABSTRACT: Gout is one of the most common forms of arthritis and the prevalence is increasing. Management comprises rapid and effective control of the inflammation in acute gout and sustained urate lowering in the long term. Improving the outcomes for cheaper old drugs and for the increasing number of new, more expensive agents is an important clinical goal. The role of pharmacogenetics in predicting response and adverse events to gout therapies is of considerable interest. Currently, prospective screening is employed to detect HLA-B*5801 carriage and glucose-6-phosphate dehydrogenase deficiency, to minimize occurrence of allopurinol hypersensitivity and pegloticase-related hemolytic anemia. In the future it is likely that other genetic markers of drug response will make the transition to clinical practice to further improve the efficacy and safety of gout therapies. In this review, we will examine the potential clinical relevance of specific genetic variants in the management of gout.

12 Review Patient Information about Gout: An International Review of Existing Educational Resources. 2015

Johnston, Megan E / Treharne, Gareth J / Chapman, Peter T / Stamp, Lisa K. ·From the Department of Medicine, University of Otago, Christchurch; Department of Psychology, University of Otago, Dunedin; Department of Rheumatology, Immunology and Allergy, Canterbury District Health Board, New Zealand.M.E. Johnston, PhD, Department of Medicine, University of Otago, Christchurch; G.J. Treharne, PhD, Department of Psychology, University of Otago, Dunedin; P.T. Chapman, MD, FRACP, Department of Rheumatology, Immunology and Allergy, Canterbury District Health Board; L.K. Stamp, MB, ChB, FRACP, PhD, Department of Medicine, University of Otago, Christchurch. ·J Rheumatol · Pubmed #25834205.

ABSTRACT: OBJECTIVE: Inadequate patient information about gout may contribute to poor disease outcomes. We reviewed existing educational resources for gout to identify strengths and weaknesses and compare resources cross-nationally. METHODS: Content, readability, and dietary recommendations were reviewed using a sample of 30 resources (print and Web-based) from 6 countries. RESULTS: More than half of the resources were written at a highly complex level. Some content areas were lacking coverage, including comorbidity risks, uric acid target levels, and continuing allopurinol during acute attacks. CONCLUSION: Our findings suggest significant room for improvement in gout patient educational resources, particularly regarding self-management.

13 Review Impaired response or insufficient dosage? Examining the potential causes of "inadequate response" to allopurinol in the treatment of gout. 2014

Stamp, Lisa K / Merriman, Tony R / Barclay, Murray L / Singh, Jasvinder A / Roberts, Rebecca L / Wright, Daniel F B / Dalbeth, Nicola. ·Department of Medicine, University of Otago, Christchurch, P.O. Box 4345, Christchurch 8140, New Zealand. Electronic address: lisa.stamp@cdhb.health.nz. · Department of Biochemistry, University of Otago, Dunedin, New Zealand. · Department of Clinical Pharmacology, Christchurch Hospital, Christchurch, New Zealand. · Medicine Service, Birmingham VA Medical Center, Birmingham, AL; Rheumatology Division, University of Alabama, Birmingham, AL. · Department of Surgical Sciences, University of Otago, Dunedin, New Zealand. · School of Pharmacy, University of Otago, Dunedin, New Zealand. · Department of Medicine, University of Auckland, Auckland, New Zealand. ·Semin Arthritis Rheum · Pubmed #24925693.

ABSTRACT: OBJECTIVES: Gout is one of the most common forms of arthritis. It is well established that urate-lowering therapy that aims for a serum urate less than at least 0.36 mmol/l (6 mg/dl) is required for the successful management of gout. Allopurinol, a xanthine oxidase (XO) inhibitor, is the most commonly used urate-lowering therapy. However, many patients fail to achieve the target serum urate on allopurinol; these patients can be considered to have "inadequate response" to allopurinol. Herein, we examine the potential mechanisms and implications of inadequate response to allopurinol. METHODS: The literature was reviewed for potential causes for failure to reach target serum urate in patients receiving allopurinol. RESULTS: The two most common causes of inadequate response to allopurinol are poor adherence and under-dosing of allopurinol. Adherent patients who fail to achieve target serum urate on standard doses of allopurinol form a group that could be considered to be "partially resistant" to allopurinol. There are four potential mechanisms for partial allopurinol resistance: decreased conversion of allopurinol to oxypurinol; increased renal excretion of oxypurinol; abnormality in XO structure and/or function such that oxypurinol is rendered less effective and/or drug interactions. CONCLUSIONS: It is important to determine the reasons for failure to achieve treatment targets with allopurinol, particularly as newer agents become available. The knowledge of the mechanisms for inadequate response may help guide the clinician towards making a therapeutic choice that is more likely to result in achieving the serum urate target.

14 Review Gout: joints and beyond, epidemiology, clinical features, treatment and co-morbidities. 2014

Robinson, Philip C / Horsburgh, Simon. ·University of Queensland Diamantina Institute, Princess Alexandra Hospital, Brisbane, Australia; Department of Rheumatology, Gold Coast University Hospital, Gold Coast, Australia. Electronic address: philip.c.robinson@gmail.com. · Department of Preventive and Social Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand. ·Maturitas · Pubmed #24880206.

ABSTRACT: Gout is a common inflammatory arthritis precipitated by an inflammatory reaction to urate crystals in the joint. Gout is increasingly being recognised as a disease primarily of urate overload with arthritis being a consequence of this pathological accumulation. It is associated with a number of important co-morbidities including chronic kidney disease, obesity, diabetes and cardiovascular disease. The prevalence of gout is increasing around the world. Significant progress has been made in determining the genetic basis for both gout and hyperuricaemia. Environmental risk factors for gout have been identified as certain foods, alcohol and several medications. There is, however, little evidence that changing these environmental risks improves gout on an individual level. Treatment of gout encompasses two strategies: firstly treatment of inflammatory arthritis with non-steroidal anti-inflammatories, corticosteroids, colchicine or interleukin-1 inhibitors. The second and most important strategy is urate lowering, to a target of 0.36 mmol/L (6 mg/dL) or potentially lower in those with tophi (collections of crystalline urate subcutaneously). Along with urate lowering, adequate and prolonged gout flare prophylaxis is required to prevent the precipitation of acute attacks. Newer urate lowering agents are in development and have the potential to significantly expand the potential treatment options. Education of patients regarding the importance of life long urate lowering therapy and prophylaxis of acute attacks is critical to treatment success as adherence with medication is low in chronic diseases in general but especially in gout.

15 Review The genetic basis of gout. 2014

Merriman, Tony R / Choi, Hyon K / Dalbeth, Nicola. ·Department of Biochemistry, University of Otago, Dunedin 9012, New Zealand. Electronic address: tony.merriman@otago.ac.nz. · Section of Rheumatology and Clinical Epidemiology Unit, Boston University School of Medicine, Boston, MA 02118, USA. · Department of Medicine, University of Auckland, Auckland 1023, New Zealand. ·Rheum Dis Clin North Am · Pubmed #24703347.

ABSTRACT: Gout results from deposition of monosodium urate (MSU) crystals. Elevated serum urate concentrations (hyperuricemia) are not sufficient for the development of disease. Genome-wide association studies (GWAS) have identified 28 loci controlling serum urate levels. The largest genetic effects are seen in genes involved in the renal excretion of uric acid, with others being involved in glycolysis. Whereas much is understood about the genetic control of serum urate levels, little is known about the genetic control of inflammatory responses to MSU crystals. Extending knowledge in this area depends on recruitment of large, clinically ascertained gout sample sets suitable for GWAS.

16 Review The global burden of gout: estimates from the Global Burden of Disease 2010 study. 2014

Smith, Emma / Hoy, Damian / Cross, Marita / Merriman, Tony R / Vos, Theo / Buchbinder, Rachelle / Woolf, Anthony / March, Lyn. ·Department of Rheumatology, Royal North Shore Hospital, Northern Clinical School, Institute of Bone and Joint Research, University of Sydney, St Leonards, New South Wales, Australia. · School of Population Health, University of Queensland, Herston, Queensland, Australia. · School of Medical Sciences, University of Otago, Dunedin, New Zealand. · School of Population Health, University of Queensland, Herston, Queensland, Australia Institute for Health Metrics and Evaluation, University of Washington, Seattle, Washington, USA. · Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia Monash Department of Clinical Epidemiology, Cabrini Hospital, Melbourne, Victoria, Australia. · Department of Rheumatology, Royal Cornwall Hospital, Truro, UK. ·Ann Rheum Dis · Pubmed #24590182.

ABSTRACT: OBJECTIVE: Gout is the most common cause of inflammatory arthritis in men, but has not previously been included in Global Burden of Disease (GBD) studies. As part of the GBD 2010 Study, the Musculoskeletal Disorders and Risk Factors Expert Group estimated the global burden of gout. METHODS: The American Rheumatism Association 1977 case definition of primary gout was used in the study. A series of systematic reviews were conducted to gather the age-specific and sex-specific epidemiological data for gout prevalence, incidence, mortality risk and duration. Two main disabling sequelae of gout were identified; acute episode gout and chronic polyarticular gout, and used in the surveys to collect data to derive disability weights. The epidemiological data together with disability weights were then used to calculate years of life lived with disability (YLDs) for gout, for 1990 and 2010. No evidence of cause-specific mortality associated with gout was found. Gout disability-adjusted life years (DALYs), therefore, have the same value as YLDs. RESULTS: Global prevalence of gout was 0.08% (95% uncertainty interval (UI) 0.07 to 0.08). DALYs increased from 76 000 (95% UI 48 to 112) in 1990 to 114 000 (95% UI 72 to 167) in 2010. Out of all 291 conditions studied in the GBD 2010 Study, gout ranked 138th in terms of disability as measured by YLDs, and 173rd in terms of overall burden (DALYs). CONCLUSIONS: The burden of gout is rising. With increasing ageing populations globally, this evidence is a significant prompt to optimise treatment and management of gout at individual, community and national levels.

17 Review Hyperuricaemia in the Pacific: why the elevated serum urate levels? 2014

Gosling, Anna L / Matisoo-Smith, Elizabeth / Merriman, Tony R. ·Department of Anatomy, Allan Wilson Centre for Molecular Ecology and Evolution, University of Otago, PO Box 913, Dunedin, New Zealand, anna.gosling@anatomy.otago.ac.nz. ·Rheumatol Int · Pubmed #24378761.

ABSTRACT: Pacific Island populations, particularly those of Polynesian descent, have a high prevalence of hyperuricaemia and gout. This is due to an inherently higher urate level among these populations with a demonstrated genetic predisposition. While an excess of urate can cause pathology, urate is also important for human health. It has been implicated as an antioxidant, has a neuroprotective role and is involved in innate immune responses. This paper provides a brief review of urate levels worldwide, with a particular focus on island Southeast Asia and the Pacific. We then present possible evolutionary explanations for the elevated serum urate levels among Pacific populations in the context of the physiological importance of urate and of the settlement history of the region. Finally, we propose that ancestry may play a significant role in hyperuricaemia in these populations and that exposure to malaria prior to population expansion into the wider Pacific may have driven genetic selection for variants contributing to high serum urate.

18 Review Systematic review of the prevalence of gout and hyperuricaemia in Australia. 2012

Robinson, P C / Taylor, W J / Merriman, T R. ·University of Queensland Diamantina Institute Department of Rheumatology, Princess Alexandra Hospital, Brisbane, Queensland, Australia University of Otago, Wellington Wellington Regional Rheumatology Unit, Hutt Valley District Health Board, Lower Hutt Department of Biochemistry, University of Otago, Dunedin, New Zealand. ·Intern Med J · Pubmed #24020339.

ABSTRACT: AIMS: Gout is a growing health problem worldwide especially in affluent countries, such as Australia. Gout and hyperuricaemia are associated with the metabolic syndrome, diabetes mellitus, obesity and hypertension. More importantly, Australia has a growing prevalence of these important health problems. The aim of this study was to systematically review published information regarding the prevalence of gout and hyperuricaemia in Australia. METHODS: A systematic search was undertaken of the MEDLINE, EMBASE and Web of Science databases, as well as relevant websites for journal articles and reports relating to the prevalence of hyperuricaemia and gout in Australia. RESULTS: Twenty-five journal articles and five reports were included in the review. Data collected in a standardised way show gout increased in prevalence from 0.5% population prevalence to 1.7% population prevalence from 1968 to 1995/1996. There has been a significant rise in the prevalence of gout in the Australian Aboriginal population from 0% in 1965 to 9.7% in men and 2.9% in women in 2002. Consistent with the rise in gout prevalence, serum uric acid in blood donors has increased from 1959 to 1980 (17% in 30- to 40-year-old men). CONCLUSIONS: The rate of gout and hyperuricaemia in Australia is high in relation to comparable countries and is increasing. The prevalence of gout in elderly male Australians is second only to New Zealand, which has the highest reported rate in the world. Further research on Aboriginal and Torres Strait Islander gout and hyperuricaemia is required as a result of the lack of contemporary data.

19 Review The genetic basis of hyperuricaemia and gout. 2011

Merriman, Tony R / Dalbeth, Nicola. ·Department of Biochemistry, University of Otago, PO Box 56, Dunedin, New Zealand. tony.merriman@stonebow.otago.ac.nz ·Joint Bone Spine · Pubmed #20472486.

ABSTRACT: Gout results from elevated urate concentrations in the blood (hyperuricaemia). When super-saturation of urate is reached, monosodium urate crystals form within the joint. In some individuals, these crystals elicit a painful self-limiting inflammatory response that is characteristic of acute gouty arthritis. The most important cause of hyperuricaemia is reduced excretion of uric acid in the urine. Uric acid excretion is coordinated by a suite of urate transport molecules expressed in the renal collecting tubules, and is a key physiological checkpoint in gout. Other checkpoints in gout are hepatic production of urate, monosodium urate crystal formation, and initiation of the acute inflammatory response. Genome-wide association scans for genes regulating serum urate concentrations have identified two major regulators of hyperuricaemia- the renal urate transporters SLC2A9 and ABCG2. The risk variants at each gene approximately double the risk for gout in people of Caucasian ancestry, with SLC2A9 also resulting in higher risk for gout in people of Polynesian ancestry, a diverse population characterized by a high prevalence of gout. Ongoing genetic association studies are identifying and confirming other genes controlling serum urate concentrations; although genome-wide association studies in gout per se await recruitment of suitable case sample sets.

20 Clinical Trial A population pharmacokinetic model to predict oxypurinol exposure in patients on haemodialysis. 2017

Wright, Daniel Fb / Doogue, Matthew P / Barclay, Murray L / Chapman, Peter T / Cross, Nicholas B / Irvine, John H / Stamp, Lisa K. ·School of Pharmacy, University of Otago, PO Box 56, Dunedin, 9054, New Zealand. dan.wright@otago.ac.nz. · Department of Medicine, University of Otago, Christchurch, New Zealand. · Department of Clinical Pharmacology, Christchurch Hospital, Christchurch, New Zealand. · Department of Rheumatology Immunology and Allergy, Christchurch Hospital, Christchurch, New Zealand. ·Eur J Clin Pharmacol · Pubmed #27683090.

ABSTRACT: PURPOSE: The aims of this study were to characterise the population pharmacokinetics of oxypurinol in patients receiving haemodialysis and to compare oxypurinol exposure in dialysis and non-dialysis patients. METHODS: Oxypurinol plasma concentrations from 6 gout people receiving haemodialysis and 19 people with gout not receiving dialysis were used to develop a population pharmacokinetic model in NONMEM. Deterministic simulations were used to predict the steady-state area under the oxypurinol plasma concentration time curve over 1 week (AUC RESULTS: The pharmacokinetics of oxypurinol were best described by a one-compartment model with a separate parameter for dialytic clearance. Allopurinol 100 mg daily produced an AUC CONCLUSIONS: Oxypurinol is efficiently removed by dialysis. The population dialytic and total (non-dialytic) clearance of oxypurinol were found to be 8.23 and 1.23 L/h, standardised to a fat-free mass of 70 kg and creatinine clearance of 6 L/h, respectively. Our results suggest that if the combination of low-dose allopurinol and haemodialysis does not result in sustained urate lowering below treatment targets (serum urate ≤0.36 mmol/L), then allopurinol doses may be increased to optimise oxypurinol exposure.

21 Article Evaluation of the diet wide contribution to serum urate levels: meta-analysis of population based cohorts. 2018

Major, Tanya J / Topless, Ruth K / Dalbeth, Nicola / Merriman, Tony R. ·Department of Biochemistry, University of Otago, 710 Cumberland Street, Dunedin 9054, New Zealand. · Department of Medicine, University of Auckland, Auckland, New Zealand. · Department of Biochemistry, University of Otago, 710 Cumberland Street, Dunedin 9054, New Zealand tony.merriman@otago.ac.nz. ·BMJ · Pubmed #30305269.

ABSTRACT: OBJECTIVE: To systematically test dietary components for association with serum urate levels and to evaluate the relative contributions of estimates of diet pattern and inherited genetic variants to population variance in serum urate levels. DESIGN: Meta-analysis of cross sectional data from the United States. DATA SOURCES: Five cohort studies. REVIEW METHODS: 16 760 individuals of European ancestry (8414 men and 8346 women) from the US were included in analyses. Eligible individuals were aged over 18, without kidney disease or gout, and not taking urate lowering or diuretic drugs. All participants had serum urate measurements, dietary survey data, information on potential confounders (sex, age, body mass index, average daily calorie intake, years of education, exercise levels, smoking status, and menopausal status), and genome wide genotypes. The main outcome measures were average serum urate levels and variance in serum urate levels. β values (95% confidence intervals) and Bonferroni corrected P values from multivariable linear regression analyses, along with regression partial R RESULTS: Seven foods were associated with raised serum urate levels (beer, liquor, wine, potato, poultry, soft drinks, and meat (beef, pork, or lamb)) and eight foods were associated with reduced serum urate levels (eggs, peanuts, cold cereal, skim milk, cheese, brown bread, margarine, and non-citrus fruits) in the male, female, or full cohorts. Three diet scores, constructed on the basis of healthy diet guidelines, were inversely associated with serum urate levels and a fourth, data driven diet pattern positively associated with raised serum urate levels, but each explained ≤0.3% of variance in serum urate. In comparison, 23.9% of variance in serum urate levels was explained by common, genome wide single nucleotide variation. CONCLUSION: In contrast with genetic contributions, diet explains very little variation in serum urate levels in the general population.

22 Article ABCG2 rs2231142 (Q141K) and oxypurinol concentrations in people with gout receiving allopurinol. 2018

Stamp, Lisa K / Wallace, Mary / Roberts, Rebecca L / Frampton, Christopher / Miner, Jeffrey N / Merriman, Tony R / Dalbeth, Nicola. ·Department of Medicine, University of Otago, Christchurch, PO Box 4345, New Zealand. Electronic address: lisa.stamp@cdhb.health.nz. · Department of Surgical Sciences, University of Otago, PO Box 56, Dunedin, New Zealand. · Department of Medicine, University of Otago, Christchurch, PO Box 4345, New Zealand. · Viscentio Bio 3550 General Atomics Court, San Diego, CA, 92121, USA. · Department of Biochemistry, University of Otago, PO Box 56, Dunedin, New Zealand. · Department of Medicine, University of Auckland, 85 Park Rd, Grafton, Auckland, 1023, New Zealand. ·Drug Metab Pharmacokinet · Pubmed #30274827.

ABSTRACT: -- No abstract --

23 Article The relationship between ferritin and urate levels and risk of gout. 2018

Fatima, Tahzeeb / McKinney, Cushla / Major, Tanya J / Stamp, Lisa K / Dalbeth, Nicola / Iverson, Cory / Merriman, Tony R / Miner, Jeffrey N. ·Department of Biochemistry, University of Otago, Dunedin, New Zealand. · Department of Medicine, University of Otago, Christchurch, New Zealand. · Department of Medicine, University of Auckland, Auckland, New Zealand. · Medical Scientific Affairs, Ironwood Pharmaceuticals, Cambridge, MA, USA. · Department of Biochemistry, University of Otago, Dunedin, New Zealand. tony.merriman@otago.ac.nz. · Biology, Ardea Biosciences, Inc., San Diego, CA, USA. ·Arthritis Res Ther · Pubmed #30111358.

ABSTRACT: BACKGROUND: Ferritin positively associates with serum urate and an interventional study suggests that iron has a role in triggering gout flares. The objective of this study was to further explore the relationship between iron/ferritin and urate/gout. METHODS: European (100 cases, 60 controls) and Polynesian (100 cases, 60 controls) New Zealand (NZ) males and 189 US male cases and 60 male controls participated. The 10,727 participants without gout were from the Jackson Heart (JHS; African American = 1260) and NHANES III (European = 5112; African American = 4355) studies. Regression analyses were adjusted for age, sex, body mass index and C-reactive protein. To test for a causal relationship between ferritin and urate, bidirectional two-sample Mendelian randomization analysis was performed. RESULTS: Serum ferritin positively associated with gout in NZ Polynesian (OR (per 10 ng ml CONCLUSIONS: These data replicate the association of ferritin with serum urate. Increased ferritin levels associated with gout and flare frequency. There was evidence of a causal effect of iron and ferritin on urate.

24 Article Mediation analysis to understand genetic relationships between habitual coffee intake and gout. 2018

Hutton, Joseph / Fatima, Tahzeeb / Major, Tanya J / Topless, Ruth / Stamp, Lisa K / Merriman, Tony R / Dalbeth, Nicola. ·Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Rd, Grafton, Auckland, New Zealand. · Department of Biochemistry, University of Otago, Dunedin, New Zealand. · Department of Medicine, University of Otago, Christchurch, New Zealand. · Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Rd, Grafton, Auckland, New Zealand. n.dalbeth@auckland.ac.nz. ·Arthritis Res Ther · Pubmed #29976226.

ABSTRACT: BACKGROUND: Increased coffee intake is associated with reduced serum urate concentrations and lower risk of gout. Specific alleles of the GCKR, ABCG2, MLXIPL, and CYP1A2 genes have been associated with both reduced coffee intake and increased serum urate in separate genome-wide association studies (GWAS). The aim of this study was to determine whether these single nucleotide polymorphisms (SNPs) influence the risk of gout through their effects on coffee consumption. METHODS: This research was conducted using the UK Biobank Resource. Data were available for 130,966 European participants aged 40-69 years. Gout status and coffee intake were tested for association with four urate-associated SNPs: GCKR (rs1260326), ABCG2 (rs2231142), MLXIPL (rs1178977), and CYP1A2 (rs2472297). Multiple regression and path analysis were used to examine whether coffee consumption mediated the effect of the SNPs on gout risk. RESULTS: Coffee consumption was inversely associated with gout (multivariate adjusted odds ratio (95% confidence interval (CI)) for any coffee consumption 0.75 (0.67-0.84, P = 9 × 10 CONCLUSION: Coffee consumption is inversely associated with risk of gout. Although alleles at several SNPs associate with both lower coffee consumption and higher risk of gout, these SNPs largely influence gout risk directly, rather than indirectly through effects on coffee consumption.

25 Article Untangling the complex relationships between incident gout risk, serum urate, and its comorbidities. 2018

Sun, Mengying / Vazquez, Ana I / Reynolds, Richard J / Singh, Jasvinder A / Reeves, Mathew / Merriman, Tony R / Gaffo, Angelo L / Los Campos, Gustavo de. ·Department of Epidemiology and Biostatistics, Michigan State University, 220 Trowbridge Rd, East Lansing, MI 48824, USA. · The Institute for Quantitative Health Science and Engineering, Michigan State University, 220 Trowbridge Rd, East Lansing, MI 48824, USA. · Division of Clinical Immunology and Rheumatology, University of Alabama Birmingham (UAB), 1825 University Blvd., Birmingham, AL 35294, USA. · Biochemistry Department, School of Biomedical Sciences, University of Otago, 710 Cumberland St., Dunedin, 9054, New Zealand. · Department of Epidemiology and Biostatistics, Michigan State University, 220 Trowbridge Rd, East Lansing, MI 48824, USA. gustavoc@msu.edu. · The Institute for Quantitative Health Science and Engineering, Michigan State University, 220 Trowbridge Rd, East Lansing, MI 48824, USA. gustavoc@msu.edu. · Department of Probability and Statistics, Michigan State University, 220 Trowbridge Rd, East Lansing, MI 48824, USA. gustavoc@msu.edu. ·Arthritis Res Ther · Pubmed #29720278.

ABSTRACT: BACKGROUND: Many gout comorbidities (e.g., hypertension) are correlated with serum urate. In this investigation, we identified risk factors (e.g., systolic blood pressure [SBP]), that (1) are associated with incident gout, (2) have effects on gout risk that cannot be fully explained by correlated differences in serum urate, and (3) may modulate the relationship between gout and serum urate. METHODS: Using data from the Atherosclerosis Risk in Communities (ARIC) study, we estimated the unadjusted associations between gout and risk factors by calculating ORs and using chi-square tests. The adjusted associations were analyzed using logistic regression by sequentially adding (1) one risk factor at a time or (2) all risk factors, to a baseline model that includes serum urate only. Stepwise selection was used to select main effects. Two-way interactions of variables from the main effects model were also analyzed. RESULTS: Average gout incidence was 2.7 per 1000 people per year. Serum urate was highly associated with incident gout, with odd ratios of 3.16 [95% CI 2.11, 4.76] and 25.9 [95% CI 17.2, 38.4] for moderately high (6-8 mg/dl) and high serum urate (> 8 mg/dl), relative to normal serum urate (< 6 mg/dl), respectively. Ethnicity and SBP were independently and additively associated with gout after accounting for serum urate levels. No significant interactions were found between serum urate and ethnicity or SBP. CONCLUSIONS: Ethnicity and hypertension are predictive of gout risk, and the associations cannot be fully explained by serum urate. For serum urate levels near the crystallization threshold (6-8 mg/dl) African Americans and people with hypertension are at two to three times greater risk for developing gout. The gout risk for this group appears to increase before the onset of severe hyperuricemia.

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