Gout in Native Hawaiian Patients in Hawai'i: Clinical Characteristics and Disparities.

OBJECTIVE: The purpose of this study was to investigate differences in clinical characteristics and health care use of Native Hawaiian and White patients with gout. METHODS: We performed a retrospective chart review of Native Hawaiian and White patients with gout treated from 2011 to 2017 within a large health care system in Hawai'i. We compared demographic characteristics, clinical outcomes, and risk factors for gout. We used multivariable logistic regression to identify predictive factors of emergency department visits. RESULTS: We identified 270 Native Hawaiian patients with gout and 239 White patients with gout. The Native Hawaiian patients were younger on average (54.0 vs 64.0 years; P < 0.0001) and had an earlier onset of disease (50.0 vs 57.0 years; P < 0.0001). Native Hawaiian patients with gout had higher mean (7.58 vs 6.87 mg/dL; P < 0.0001) and maximum (10.30 vs 9.50 mg/dL; P < 0.0001) serum urate levels compared to White patients with gout. Native Hawaiian patients with gout also had a greater number of tophi (median 2.00 vs 1.00; P < 0.0001). Native Hawaiians patients with gout were 2.7 times more likely to have frequent (≥1) emergency department visits than White patients with gout. Native Hawaiian patients with gout were less likely to have a therapeutic serum urate ≤6.0 mg/dL and had lower rates of rheumatology specialty care. CONCLUSION: Native Hawaiian patients have a higher disease burden of gout, with earlier disease onset and more tophi. Native Hawaiian patients with gout are more likely to use emergency services for gout and have lower rates of rheumatology specialty care compared to White patients. Future studies are needed to promote culturally appropriate preventive care and management of gout in Native Hawaiians.

Trends in Prevalence of Gout Among US Asian Adults, 2011-2018.

Importance: Gout disparities among Black individuals in the US have recently been explained by socioclinical factors; however, no information is available among Asian individuals living in Western countries, despite their disproportionately worsening metabolic health. Objective: To determine the prevalence of gout and serum urate concentrations according to race and ethnicity and to explore the association of social determinants of health and clinical factors. Design, Setting, and Participants: This is a population-based, cross-sectional analysis. Data from a nationally representative sample of US adults were obtained from the National Health and Nutrition Examination Survey (NHANES) (2011-2018) in which Asian race data were collected (primary). Data from the UK Biobank (2006-2021) were used for replication of the Asian vs White differences. Data analysis was performed from December 2021 to September 2022. Main Outcomes and Measures: Race-specific gout prevalence and serum urate levels. Results: A total of 22 621 participants from NHANES (2011-2018) were included in the analysis (mean [SD] age, 49.8 [17.8] years; 10 948 male participants [48.4%]). In 2017 to 2018, gout affected 12.1 million US individuals, with its crude prevalence increasing from 3.6% (95% CI, 2.8%-4.5%) in 2011 to 2012 to 5.1% (95% CI, 4.2%-5.9%) in 2017 to 2018 (P for trend = .03); this trend was no longer significant after age adjustment (P for trend = .06) or excluding Asian individuals (P for trend = .11). During the same period, age- and sex-adjusted prevalence among Asian Americans doubled from 3.3% (95% CI, 2.1%-4.5%) to 6.6% (95% CI, 4.4%-8.8%) (P for trend = .007) to numerically exceed all other racial and ethnic groups in 2017 to 2018, with age- and sex-adjusted odds ratio (ORs) of 1.61 (95% CI, 1.03-2.51) and a socioclinical factor-adjusted multivariable OR of 2.62 (95% CI, 1.59-4.33) for Asian vs White individuals. The latest age- and sex-adjusted gout prevalence among US individuals aged 65 years and older was 10.0% among White individuals and 14.8% among Asian individuals (including 23.6% of Asian men). Serum urate concentrations also increased between 2011 and 2018 among US Asian individuals (P for trend = .009). The Asian vs White disparity was also present in the UK Biobank. Conclusions and Relevance: The findings of this study suggest that the prevalence of gout among Asian individuals numerically surpassed that for all other racial and ethnic groups in 2017 to 2018. This Asian vs White disparity did not appear to be associated with socioclinical factors.

Nationwide racial/ethnic disparities in US emergency department visits and hospitalizations for gout.

OBJECTIVES: Gout prevalence is reportedly ∼20% higher in US Black adults than Whites, but racial differences in emergency department (ED) visits and hospitalizations for gout are unknown. We evaluated the latest US national utilization datasets according to racial/ethnic groups. METHODS: Using 2019 US National Emergency Department Sample and National Inpatient Sample databases, we compared racial/ethnic differences in annual population rates of ED visits and hospitalizations for gout (primary discharge diagnosis) per 100 000 US adults (using 2019 age- and sex-specific US census data). We also examined rates of ED visits and hospitalizations for gout among all US ED visits/hospitalizations and mean costs for each gout encounter. RESULTS: Compared with White patients, the per capita age- and sex-adjusted rate ratio (RR) of gout primary ED visits for Black patients was 5.01 (95% CI 4.96, 5.06), for Asian patients 1.29 (1.26, 1.31) and for Hispanic patients 1.12 (1.10, 1.13). RRs for gout primary hospitalizations were 4.07 (95% CI 3.90, 4.24), 1.46 (1.34, 1.58) and 1.06 (0.99, 1.13), respectively. Corresponding RRs among total US hospitalizations were 3.17 (95% CI 2.86, 3.50), 3.23 (2.71, 3.85) and 1.43 (1.21, 1.68) and among total ED visits were 2.66 (95% CI, 2.50, 2.82), 3.28 (2.64, 4.08), and 1.14 (1.05, 1.24), respectively. RRs were largest among Black women. Costs for ED visits and hospitalizations experienced by race/ethnicity showed similar disparities. CONCLUSIONS: These first nationwide data found a substantial excess in both gout primary ED visits and hospitalizations experienced by all underserved racial/ethnic groups, particularly by Black women, revealing an urgent need for improved care to eliminate inequities in gout outcomes.

The disproportionately large contribution of the Maori and Pacific Islander community to the healthcare burden of gout in Western Sydney.

BACKGROUND: Gout is a common chronic inflammatory disorder due to monosodium urate deposition, which results in severe inflammatory arthritis. It is particularly common in those of Maori or Pacific Islander heritage. There is a significant number of this at-risk ethnic group in western Sydney. AIMS: To determine the healthcare burden of gout in Western Sydney. METHODS: We characterised patients managed in the emergency departments (EDs) of the four Western Sydney Local Health District (WSLHD) hospitals and those admitted for gout as the primary or secondary diagnosis from 1 January 2017 to 31 December 2018. RESULTS: There were 472 patients managed in ED on 552 occasions at a direct cost to the LHD of A$367 835. Those of Maori or Pacific Islander ethnicity comprised 25.2% (n = 119/472), while half (n = 39/80) of those managed in ED for gout on two or more occasions were of Maori or Pacific Islander ethnicity. Overall, 310 patients were admitted with gout as the principal diagnosis on 413 occasions at a cost of A$1.73 million. Seventy-five (24.2%) of the 310 patients were of Maori or Pacific Islander heritage. A total of 584 WSLHD inpatients had gout as a secondary diagnosis. This was associated with 714 admissions. CONCLUSIONS: The disproportionately large healthcare burden of gout in Western Sydney from the relatively small Maori and Pacific Islander population needs attention. Urgent culturally appropriate interventions to address gout are required to address this inequality.

A Polynesian-specific copy number variant encompassing the MICA gene associates with gout.

Gout is of particularly high prevalence in the Maori and Pacific (Polynesian) populations of Aotearoa New Zealand (NZ). Here, we investigated the contribution of common population-specific copy number variation (CNV) to gout in the Aotearoa NZ Polynesian population. Microarray-generated genome-wide genotype data from Aotearoa NZ Polynesian individuals with (n = 1196) and without (n = 1249) gout were analyzed. Comparator population groups were 552 individuals of European ancestry and 1962 of Han Chinese ancestry. Levels of circulating major histocompatibility complex (MHC) class I polypeptide-related sequence A (MICA) were measured by enzyme-linked immunosorbent assay. Fifty-four CNV regions (CNVRs) appearing in at least 10 individuals were detected, of which seven common (>2%) CNVRs were specific to or amplified in Polynesian people. A burden test of these seven revealed associations of insertion/deletion with gout (odds ratio (OR) 95% confidence interval [CI] = 1.80 [1.01; 3.22], P = 0.046). Individually testing of the seven CNVRs for association with gout revealed nominal association of CNVR1 with gout in Western Polynesian (Chr6: 31.36-31.45 Mb, OR = 1.72 [1.03; 2.92], P = 0.04), CNVR6 in the meta-analyzed Polynesian sample sets (Chr1: 196.75-196.92 Mb, OR = 1.86 [1.16; 3.00], P = 0.01) and CNVR9 in Western Polynesian (Chr1: 189.35-189.54 Mb, OR = 2.75 [1.15; 7.13], P = 0.03). Analysis of European gout genetic association data demonstrated a signal of association at the CNVR1 locus that was an expression quantitative trait locus for MICA. The most common CNVR (CNVR1) includes deletion of the MICA gene, encoding an immunomodulatory protein. Expression of MICA was reduced in the serum of individuals with the deletion. In summary, we provide evidence for the association of CNVR1 containing MICA with gout in Polynesian people, implicating class I MHC-mediated antigen presentation in gout.

Unique Considerations for the Management of Gout in the Hmong Population: Examining Tertiary Encounters at a Large Regional Health Care System.

OBJECTIVE: To evaluate demographic characteristics, care encounters, comorbidities, and clinical differences in Hmong and non-Hmong patients with gout. METHODS: Using retrospective chart review, all inpatient encounters (Hmong versus non-Hmong) were reviewed from 2014 to 2017. Acute or chronic gout was the primary or secondary diagnosis for the encounter. RESULTS: Hmong gout patients were on average 11 years younger than non-Hmong patients, but after adjustment for age, sex, and type of encounter, they had similar rates of hypertension, diabetes mellitus, and heart disease. Hmong patients had significantly decreased renal function at the time of presentation; the odds ratio of chronic kidney disease for Hmong patients was 2.33 versus 1.48 for non-Hmong patients (P < 0.05), the mean creatinine level was 3.3 mg/dl versus 2.0 mg/dl (ß = 1.35, P < 0.001), and the glomerular filtration rate was 44.8 ml/minute versus 49.3 ml/minute (ß = -6.95, P < 0.001). Hmong gout patients were more likely to use emergency care versus elective or urgent care, they were less likely to be using medications for the treatment of gout prior to admission (32.3% versus 58.2%), and the length of hospital stay was increased (8.8 versus 5.2 days; P < 0.05). CONCLUSION: Hmong gout patients who had a tertiary care encounter were 11 years younger than non-Hmong patients with similar rates of comorbidities but had worse renal function despite the age differences. They were more likely to use emergency services, to be insured through Medicaid, and not to use preventive medications for gout prior to their encounter. Intensive efforts are needed in the Hmong population for culturally appropriate preventive care management of gout along with diabetes mellitus, hypertension, heart disease, and kidney disease.

Staying moving, staying strong: Protocol for developing culturally appropriate information for Aboriginal people with osteoarthritis, rheumatoid arthritis, lupus and gout.

INTRODUCTION: Addressing disparities in arthritis care is an important yet unmet health need for Aboriginal and Torres Strait Islander people in Australia (respectfully Aboriginal people herewith). Despite the significant prevalence and burden of arthritis within Aboriginal communities, access to care for arthritis is low. One means to reduce existing disparities in health care is to address current challenges relating to the appropriateness and acceptability of health care information resources for Aboriginal people. Health information sources can help to empower patients and their families to have greater involvement in their care and to engage in self-management of their condition. Despite an extensive range of arthritis information resources being available, currently no resources have been culturally adapted and developed in collaboration with Aboriginal consumers with arthritis. This paper outlines the processes that will be undertaken within the Staying Moving, Staying Strong project. This project aims to develop culturally secure arthritis information for Aboriginal people with osteoarthritis, rheumatoid arthritis, lupus and gout. METHODS AND ANALYSIS: The overarching principle guiding this project is cultural security, referring to the incorporation of processes such that the research will not compromise the cultural rights, values and expectations of Aboriginal people. This project will prioritise partnerships, community engagement, community benefit, sustainability, transferability, and capacity building and therefore uphold the cultural rights and values of Aboriginal people. In this six-phase project we will; 1) Establish a community reference group and advisory committee; 2) Explore the health information needs and preferences of Aboriginal people with arthritis; 3) Synthesise the existing key recommendations in high quality clinical practice guidelines on arthritis care; 4) Culturally adapt key clinical recommendations; 5) Develop culturally appropriate arthritis resources and; 6) Qualitatively evaluate the developed resources.

An enquiry into the crippling gout affecting Pacific Islander and Maori men in Western Sydney.

AIM: Despite the effectiveness and availability of urate-lowering therapies (ULT), we continue to see a number of advanced cases of tophaceous gout in the Pacific Islander and Maori population in Western Sydney. Although the high prevalence and increased severity of gout in this cohort has been well documented, there has been little qualitative research undertaken in Australia into the lived experience of this group of people. It is this gap in the research that our study aimed to address. METHODS: Participants were recruited from the rheumatology clinics at Westmead and Blacktown Hospitals. Those eligible to participate were Pacific Islander and Maori patients with tophaceous gout currently living in the Western Sydney Local Health District (WSLHD). Data collection took the form of 10 semi-structured interviews, which were subsequently transcribed verbatim. A thematic analysis of the data was then performed. RESULTS: Thematic analysis identified 6 key themes: lack of understanding of the disease and its potential effects; missed opportunities for intervention and disjointed care; chronic reliance upon corticosteroids; trivialization of gout as a nuisance illness; the substantial financial impact of chronic illness; and the all-consuming nature of severe gout. CONCLUSION: The human cost of severe tophaceous gout in this cohort is immense. All 10 participants exemplified the disease's devastating social effects. We propose 4 key recommendations: improved education regarding diagnosis and management; immediate prescription of ULT at first presentation; a lower threshold for out-of-hospital rheumatologist referral; and improved follow-up through a nurse- and pharmacist-led collaborative gout management program.

The inequity of access to health: a case study of patients with gout in one general practice.

AIM: Gout is a health equity issue for Maori and Pacific peoples because disparities in quality of care exist. This study aims to describe domains of access that may contribute to the optimisation of gout care and, therefore, address health inequity. METHODS: The practice management system at one general practice in Auckland was used to identify enrolled patients with gout, using disease codes and medication lists. Barriers to access for the cohort were investigated using staff knowledge and the practice management system. The general practice is uniquely situated within an urban marae (traditional meeting house) complex serving a predominantly Maori community. This enables a focus on domains of access other than cultural safety. RESULTS: Of 3,095 people enrolled at the practice, 268 were identified as having gout. Of these, 94% had at least one other long-term health condition. The majority of people with gout enrolled at the practice have employment roles incongruent with the clinic's opening hours. CONCLUSIONS: Social circumstances, such as employment and availability of transport, should be actively discussed with all patients and recorded in the practice management system. Reorientation of health services, including hours of access, is evidentially required to ensure optimal management of gout and possibly other health conditions.

Gout prevalence in the Hmong: a prime example of health disparity and the role of community-based genetic research.

Individuals of distinct Asian backgrounds are commonly aggregated as Asian, which could mask the differences in the etiology and prevalence of health conditions in the different Asian subgroups. The Hmong are a growing Asian subgroup in the United States with a higher prevalence of gout and gout-related comorbidities than non-Hmong. Genetic explorations in the Hmong suggest a higher prevalence of genetic polymorphisms associated with an increased risk of hyperuricemia and gout. History of immigration, acculturation, lifestyle factors, including dietary and social behavioral patterns, and the use of traditional medicines in the Hmong community may also increase the risk of developing gout and lead to poor gout management outcomes. Engaging minorities such as the Hmong population in biomedical research is a needed step to reduce the burden of health disparities within their respective communities, increase diversity in genomic studies, and accelerate the adoption of precision medicine to clinical practice.

People of different Asian heritage are commonly grouped as Asian, which could mask the differences in the causes and rates of specific health conditions in the different Asian subgroups. The Hmong are a growing Asian group in the United States with higher gout rates and gout-related conditions than non-Hmong. Genetic research in the Hmong suggests higher rates of genetic changes associated with higher urate levels and increased gout risk. The immigration to the United States and adaptation to the Western lifestyle could also affect the Hmong's risk for developing elevated urate levels and gout. Some lifestyle factors, including dietary and social behavioral patterns, and the use of traditional medicines in the Hmong, may also increase their risk of developing gout and lead to poor gout management. Engaging minorities such as the Hmong population in clinical research is a needed step to reduce the burden of health disparities within their respective communities, increase diversity in genetic studies, and widen the application of precision medicine to clinical practice.

The association between genetic polymorphisms in ABCG2 and SLC2A9 and urate: an updated systematic review and meta-analysis.

BACKGROUND: Replication studies showed conflicting effects of ABCG2 and SLC2A9 polymorphisms on gout and serum urate. This meta-analysis therefore aimed to pool their effects across studies. METHODS: Studies were located from MEDLINE and Scopus from inception to 17th June 2018. Observational studies in adults with any polymorphism in ABCG2 or SLC2A9, and outcome including gout, hyperuricemia, and serum urate were included for pooling. Data extractions were performed by two independent reviewers. Genotype effects were pooled stratified by ethnicity using a mixed-effect logistic model and a multivariate meta-analysis for dichotomous and continuous outcomes. RESULTS: Fifty-two studies were included in the analysis. For ABCG2 polymorphisms, mainly studied in Asians, carrying 1-2 minor-allele-genotypes of rs2231142 and rs72552713 were respectively about 2.1-4.5 and 2.5-3.9 times higher odds of gout than non-minor-allele-genotypes. The two rs2231142-risk-genotypes also had higher serum urate about 11-18 µmol/l. Conversely, carrying 1-2 minor alleles of rs2231137 was about 36-57% significantly lower odds of gout. For SLC2A9 polymorphisms, mainly studied in Caucasians, carrying 1-2 minor alleles of rs1014290, rs6449213, rs6855911, and rs7442295 were about 25-43%, 31-62%, 33-64%, and 35-65% significantly lower odds of gout than non-minor-allele-genotypes. In addition, 1-2 minor-allele-genotypes of the latter three polymorphisms had significantly lower serum urate about 20-49, 21-51, and 18-54 µmol/l than non-minor-allele-genotypes. CONCLUSIONS: Our findings should be useful in identifying patients at risk for gout and high serum urate and these polymorphisms may be useful in personalized risk scores. TRIAL REGISTRATION: PROSPERO registration number: CRD42018105275 .

Gender and Ethnic Inequities in Gout Burden and Management.

Although effective and low-cost urate-lowering therapy has been available for decades, inequities in gout management exist. Despite high impact of disease, rates of urate-lowering therapy prescription are low in women, in African-Americans in the United States, in Maori (Indigenous New Zealanders), and in Pacific peoples living in Aotearoa/New Zealand. Social determinants of health, barriers to accessing the health care system, health literacy demands, stigmatization, and bias contribute to inequities in gout burden and management. Approaches that focus on building health literacy and delivering culturally safe care lead to improved outcomes in gout, and offer important solutions to achieve health equity.

Gout epidemiology and comorbidities.

OBJECTIVE: To review the epidemiology of gout and associated comorbidities. METHODS: We review the key published studies of the epidemiology of gout and associated comorbidities. RESULTS: The prevalence of gout ranged 1-4% worldwide and incidence ranged 0.1-0.3%. Gout is more common in men vs. women by 3:1 to 10:1. Gout incidence and prevalence increased by each decade of life, with prevalence increasing to 11-13% and incidence increasing to 0.4% in people older than 80 years. Racial minorities in the U.S., New Zealand Maori, Han Chinese and some ethnic groups in Asia have a higher prevalence of gout. Comorbidities are common in people with gout and complicate its management and disease outcomes. Hypertension is present in up to three-quarters of gout patients and could be in the causal pathway of its association with cardiovascular disease and stroke. Chronic kidney disease of stage 3 or greater severity is present in many patients with gout. Appropriate management can improve both gout and stabilize chronic kidney disease. Whether the association of gout with metabolic syndrome and diabetes is causal is still controversial. Given the biological anti-oxidant effect of serum urate, the association of gout with neurodegenerative disorders is being actively explored. CONCLUSIONS: Gout is the most common inflammatory arthritis in adults worldwide, with a disproportionate burden of disease in men, the elderly and racial/ethnic minorities. Comorbidities in gout are very common and add further to the disease morbidity and make its management challenging.

Cost-effectiveness of sequential urate lowering therapies for the management of gout in Singapore.

Aims: Allopurinol is the most common urate lowering therapy (ULT) used to treat gout but may cause life-threatening severe cutaneous adverse reactions (SCAR) in a small number of patients. Risk of SCAR is increased for patients with the HLA-B*58:01 genotype. When alternative ULT is required, febuxostat or probenecid are recommended. The aim of this study was to conduct a cost-utility analysis of sequential ULT treatment strategies for gout, including strategies with and without HLA-B*58:01 genotyping prior to treatment initiation, with a view to inform optimal gout management in Singapore.Materials and methods: A Markov model was developed from the Singapore healthcare payer perspective. Reflecting local practice, 12 different treatment strategies containing at least one ULT (allopurinol, febuxostat, probenecid) were evaluated in adults with gout. Response rates (SUA < 6mg/dL) were derived from an in-house network meta-analysis and from published literature. Incremental cost-effectiveness ratios (ICERs) were calculated over a 30-year time horizon, with costs and benefits discounted at 3% per annum. Sensitivity analyses were conducted to explore uncertainties.Results: Sequential treatment of allopurinol 300 mg/day-allopurinol 600 mg/day-probenecid ("standard of care") was cost-effective compared to no ULT, with an ICER of SGD1,584/QALY. Allopurinol300-allopurinol600-probenecid-febuxostat sequence compared to allopurinol300-allopurinol600-probenecid had an ICER of SGD11,400/QALY. All other treatment strategies were dominated by preceding strategies. Treatment strategies incorporating HLA-B*58:01 genotyping before ULT use were dominated by the corresponding non-genotyping strategy.Conclusions: Current standard of care (allopurinol300-allopurinol 600-probenecid) for gout is cost-effective compared with no ULT in the local context. Febuxostat is unlikely to be cost-effective in Singapore at current prices unless it is used last-line.

Disseminated cutaneous gout: a rare manifestation of a common disease.

Disseminated cutaneous gout is a rare atypical cutaneous manifestation of gout in which widespread dermal and subcutaneous tophi develop at extra-articular body sites. Given the lack of joint involvement that is typically a feature in tophaceous gout, the diagnosis may not be initially suspected. We present the case of a 50-year-old Hispanic man with poorly controlled gout who was evaluated for several years of firm papulonodules over the trunk and upper and lower extremities, sparing the joints; histopathology confirmed, the diagnosis of disseminated cutaneous gout. Per our literature review, disseminated cutaneous gout presents with polymorphous papules and nodules that can mimic other, more common cutaneous diseases. There is a preponderance of cases in males, Asians, and patients with longstanding gout. The lower extremities are involved in nearly all reports. Uric acid-lowering therapy with allopurinol has been reported to decrease the size and number of lesions in a minority of treated patients.

The prevalence of the gout-associated polymorphism rs2231142 G>T in ABCG2 in a pregnant female Filipino cohort.

Gout is a metabolic disorder and one of the most common arthritic conditions. Hyperuricemia is the hallmark of developing gout and mostly caused by uric acid underexcretion. Gout disproportionately affects people of specific races and ethnicities. Filipinos are the second-largest Asian population in the USA and reported to have a higher prevalence of gout and hyperuricemia than non-Filipino counterparts and Filipinos residing in the Philippines. The genetic polymorphism rs2231142 G>T in the ABCG2 has been strongly associated with hyperuricemia and gout across multiple populations. However, the prevalence of this variant in Filipinos is unknown. Therefore, assessing the prevalence of this variant may provide insights on the high prevalence of hyperuricemia and gout in Filipinos. A total of 190 DNA samples from pregnant females who self-identified as a Filipino from the Hawaii Biorepository Bank were genotyped for rs2231142 G>T in the ABCG2. The prevalence of the gout risk allele (T) (46%) was significantly higher in Filipinos than in samples of Caucasians (12%, p < 0.001), Han Chinese (29%, p = 0.014), and African Americans (3%, p < 0.001). Similarly, the prevalence of the gout-risk genotype (TT) (21%) was significantly higher in Filipinos than in samples of Caucasians (1%, p < 0.001), Han Chinese (9%, p = 0.002), and African Americans (0.1%, p < 0.001). Though there were no gout cases in this cohort, these findings are suggestive of a genetic basis to the high prevalence of hyperuricemia and gout in Filipinos. This might also explain the reported reduced urinary uric acid excretion in Filipinos compared with Caucasians. Key Points • The Filipinos have the highest prevalence of the gout-associated risk allele (T) of the rs2231142 G>T in ABCG2. • The high prevalence of the risk allele (T) of the rs2231142 G>T in ABCG2 may partly explain the reduced urinary urate excretion and early-onset gout in Filipinos. • The high prevalence of the risk allele (T) of the rs2231142 G > T in ABCG2 may predispose Filipinos to hyperuricemia and gout when acculturated to high-purine diet.

Population-specific factors associated with fractional excretion of uric acid.

BACKGROUND: Reduced renal clearance of uric acid is a major contributor to hyperuricemia. The aim of this study was to examine clinical and genetic variables associated with fractional excretion of uric acid (FEUA). METHODS: Participants (with and without gout) in the Genetics of Gout in Aotearoa study with available genotyping and FEUA data were included (n = 1713). Ten FEUA-associated loci detected within a genome-wide association study for serum urate in a European population were analysed. A polygenic score for FEUA was calculated in each ancestry group to model the cumulative effects of the genetic variants on FEUA. Associations between FEUA and both clinical variables and polygenic score were tested using linear regression models. RESULTS: The mean (SD) FEUA was 5.13 (2.70) % in Eastern Polynesian participants, 4.70 (5.89) % in Western Polynesian participants, and 5.89 (2.73) % in New Zealand European participants. Although association with FEUA was observed for SLC2A9 rs11942223 in New Zealand European participants (P = 2.39 × 10- 8), this association was not observed in Eastern or Western Polynesian participants. The polygenic score was positively associated with FEUA in all ancestry groups. In New Zealand European participants, body mass index, diuretic use, polygenic score, and male sex were associated with FEUA and explained 22% of FEUA variance in the regression model. In Eastern and Western Polynesian participants, the tested variables explained 10% and 4% of FEUA variance respectively. CONCLUSIONS: Both clinical and genetic variables contribute to renal clearance of uric acid. SLC2A9 exerts effects on FEUA variance in people of European ancestry, but not in those of Polynesian ancestry. There is a large unexplained variance in FEUA, particularly in people of Polynesian ancestry.

Gender-specific risk factors for gout: a systematic review of cohort studies.

BACKGROUND: Though gout is more prevalent in men than women, it remains unclear whether gender influences risk factors for incident gout. We aimed to systematically review all cohort studies examining risk factors for the development of gout by gender. METHODS: MEDLINE, EMBASE, CINAHL and the Cochrane Library were searched from inception to March 2019. Risk factors for gout examined were: age, ethnicity, consumption of alcohol, meat, seafood, dairy products, purine-rich vegetables, coffee and fructose, vitamin C intake, the Dietary Approaches to Stop Hypertension (DASH) diet, metabolic syndrome, BMI, waist and chest circumference, waist-to-hip ratio, weight change, diabetes mellitus, dyslipidaemias, renal disease, psoriasis, hypertension, diuretic use and anti-diabetic medication. Cohort studies were included if examining (at least) one of these risk factors for gout in either gender in the general population or primary care. Sample characteristics from included articles and their reported risk estimates were described using narrative synthesis. RESULTS: Thirty-three articles were included, 20 (60.6%)directly compared risk factors by gender, 10 (30.3%) used men-only samples, 3 (9.1%) used women-only samples. Articles comparing risk across genders found similar increases in most risk factors. However, in men, metabolic syndrome (Hazard Ratio (95% CI) 1.37(1.20-1.58)) presented a risk of incident gout compared to none in women (> 50 years 1.15(0.85-1.54); ≤50 years 1.29(0.76-2.17)). Compared to men, women showed greater associated risk with higher consumption of fish and shellfish (HR (95% CI) Men: 1.02 (0.86-1.22); Women 1.36 (1.12-1.65)). CONCLUSIONS: Risk factors for developing gout did not typically differ between genders and therefore similar preventative advice can be provided. Exceptions were metabolic syndrome in men and excessive seafood consumption in women, but these singular articles need further examination and in general more research into the risk factors for gout which includes women is required.

Validity and reliability of the Gout Impact Scale in a multi-ethnic Asian population.

OBJECTIVES: The emphasis on capturing patient-reported outcomes (PRO) is increasing, but gout-specific PRO are lacking. We evaluated the reliability and validity of the 24-item Gout Impact Scale (GIS) of the Gout Assessment Questionnaire 2.0 (GAQ2.0) in a multi-ethnic Asian population. METHODS: Participants with gout in an academic medical center in Singapore completed the GIS which comprises five scales. Confirmatory factor analyses (CFA) were performed. Known-groups validity, divergent validity and internal consistency were evaluated. RESULTS: We analyzed data of 267 participants (mean [SD] age 52.2 [16.08] years, 92.1% men and 76.0% Chinese). CFA based on the original GIS factor structure had good model fit based on Tucker-Lewis Index (TLI) of 0.946 but not when based on Root Mean Square Error Of Approximation (RMSEA), which was 0.123 (90% CI: 0.116-0.130). Internal consistency of GIS exceeded 0.7 in all except one scale, consistent with previous studies. Hypotheses related to known-groups validity were largely supported. Scores were significantly higher (ie greater impact) for participants reporting at least some problem on the EQ-5D-3L anxiety/ depression item across all GIS scales. Correlations between RAND-36 Physical Functioning (PF) scale and all five scales in the GIS were poor (Spearman rank correlation coefficients: -0.2355 to 0.0426), implying that GIS does not measure impact of gout on physical health. CONCLUSION: The GIS is valid and reliable for assessing gout-specific psychosocial functioning in a multi-ethnic Asian population.