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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.

Objective: Gout typically responds well to medications, but adherence might be improved by education that meets individuals' needs in a way that is inclusive of their ethnicity and rurality. The aim of this study was to compare education preferences of Māori and New Zealand European (NZEuropean) individuals with gout, and of those living in rural or urban areas., Methods: People with gout managed in primary care were recruited from 2 rural regions and 1 city within Aotearoa/New Zealand. Focus groups were held with 26 Māori and 42 NZEuropean participants (44 rural, 24 urban). Participants discussed education preferences for diet, medication, and ways of communicating. The nominal group technique was employed, whereby the group compiled a list of ideas and then participants individually ranked the 3 most important ideas for each topic., Results: The most frequently prioritized ideas for the 3 topics were knowing one's own food triggers, knowing side effects of medications, and communicating via a general practitioner (GP) or specialist. More Māori participants prioritized natural remedies, easy to understand information, and communicating via television. More NZEuropean participants prioritized knowing the kinds of alcohol that trigger gout, communicating via GP/specialist, and receiving written information. More urban participants prioritized knowing to stay hydrated and medication doses as important information., Conclusion: Māori and NZEuropean individuals with gout report different understandings and education preferences around personal triggers of gout, treatment options, and ways of receiving information about gout. Further research is required to develop ethnicity-specific gout education resources internationally., (© 2017, American College of Rheumatology.)

Purpose: African Americans have a substantially higher prevalence of risk factors for gout than Caucasians. The aim of the present study was to compare the risk for incident gout among African Americans and Caucasians., Methods: Incidence rates of physician-diagnosed gout among 11,559 Caucasian men and 931 African American men aged 35 to 57 years and at high cardiovascular risk, observed for 7 years as a part of the Multiple Risk Factor Intervention Trial, were analyzed. Cox regression models were used to account for potential confounding by age, body mass index, diuretic use, hypertension and diabetes status, aspirin and alcohol consumption, and kidney disease., Results: At baseline, after accounting for risk factors, African Americans had a 14% lower prevalence of hyperuricemia than Caucasians. Incidence of gout increased with increasing prevalence of risk factors in both Caucasians and African Americans. Ethnic disparities in incidence rates were most apparent among those without other risk factors for gout. In separate Cox regression models, after accounting for risk factors, African American ethnicity was associated with a hazard ratio of 0.78 (95% confidence interval [CI], 0.66-0.93) for physician-diagnosed gout and 0.88 (95% CI, 0.85-0.90) for incident hyperuricemia. Significant interactions were observed; the association was the strongest (hazard ratio 0.47; 0.37-0.60). These associations were unaffected by addition of serum urate as a covariate or by using alternate case definitions for gout., Conclusions: After accounting for the higher prevalence of risk factors, African American ethnicity is associated with a significantly lower risk for gout and hyperuricemia compared with Caucasian ethnicity., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: In New Zealand, gout disproportionately affects Māori and Pacific people who also experience symptoms at an earlier age. Gout occurs predominantly in men and is associated with cardiovascular disease, diabetes, and renal disease. The impact on daily social activities, family, and work is enormous, and many people remain inadequately treated., Objectives: The objectives of this study were to explore the knowledge and perceptions of people with gout toward the disease and to determine the impact gout has on lifestyle including possible barriers to treatment., Methods: Sixty people with gout from the Auckland and Waikato regions of New Zealand were invited to participate in 30-minute semistructured interviews. The data were analyzed using a general inductive thematic approach., Results: Although 85% of participants were aware of dietary triggers of gout, these were not always avoided. Less than 50% knew something about how their medicines worked, and only 33% knew which medicines to use both acutely and chronically. The negative impact of gout episodes was noted through the number participants unable to work or participate in family activities. Healthcare professionals were not always the main source of information, which is an area that could be developed to improve knowledge about gout., Conclusions: There were substantial gaps in the knowledge about gout and its causes and management. All healthcare providers could help identify patients with suboptimal knowledge and improve the management of gout.

Introduction: The C allele of the nonsynonymous Arg265His (rs3733591) variant of SLC2A9 confers risk for gout in Han Chinese, Solomon Island and Japanese samples, with a stronger role in tophaceous gout. There is no evidence for an association with gout in Caucasian populations. In the present study, we tested rs3733591 for association with gout in New Zealand (NZ) Māori, Pacific Island and Caucasian samples., Methods: Rs3733591 was genotyped across gout patients (n = 229, 232 and 327 NZ Māori, Pacific Island and Caucasian samples, respectively) and non-gout controls (n = 343, 174 and 638 Māori, Pacific Island and Caucasian samples, respectively). Further Caucasian sample sets consisting of 67 cases and 4,712 controls as well as 153 cases and 6,969 controls were obtained from the Framingham Heart Study and the Atherosclerosis Risk in Communities study, respectively. The Polynesian samples were analyzed according to Eastern and Western Polynesian ancestry., Results: No evidence for risk conferred by the C allele of rs3733591 with gout was found in the sample sets of NZ Māori (odd ratio (OR) = 0.98, P = 0.86), Eastern Polynesians (OR = 0.99, P = 0.92), Western Polynesians (OR = 1.16, P = 0.36) or combined Caucasians (OR = 1.15, P = 0.13). The C allele was significantly overrepresented in Māori tophaceous cases compared to cases without tophi (OR = 2.21, P = 0.008), but not in the other ancestral groupings., Conclusions: Noting that our study's power was limited for detecting weak genetic effects, we were unable to replicate associations of rs3733591 with gout in Eastern Polynesian, Western Polynesian and Caucasian samples. However, consistent with a previous study of Han Chinese and Solomon Island populations, our data suggest that rs3733591 could be a marker of severe gout in some populations. Our results also suggest that the effect of this variant is population-specific, further confirming population heterogeneity regarding the association of SLC2A9 with gout.

Genetic variation in ABCG2 (rs2231142, Q141K), encoding a uric acid transporter, is associated with gout in diverse populations. The aim of this study was to examine a role for ABCG2 in gout susceptibility in New Zealand Māori, Pacific Island and Caucasian samples. Patients (n = 185, 173 and 214, for Māori, Pacific Island and Caucasian, respectively) satisfied the American College of Rheumatology gout classification criteria. The comparison samples comprised 284, 129 and 562 individuals, respectively, without gout. rs2231142 was genotyped and stratification accounted for using genomic control markers. Association of the minor allele of rs2231142 with gout was observed in the Pacific Island samples (OR = 2.80, P(STRAT) < 0.001 after accounting for effects of population structure), but not in the Māori samples (OR = 1.08, P(STRAT)= 0.70), with heterogeneity in association evident between the Māori and Pacific Island datasets (P(HET) = 0.001). A similar dichotomy in association was observed when samples were stratified into Western (Tonga, Samoa, Niue, Tokelau) versus Eastern Polynesian (Māori, Cook Island) origin (OR = 2.59, P(STRAT) < 0.001; OR = 1.12, P(STRAT)= 0.48, respectively; P(HET) = 0.005). Association with gout was observed in the Caucasian samples (OR = 2.20, P = 3.2 × 10(-8)). Unlike SLC2A9, which is a strong risk factor for gout in both Māori and Pacific Island people, ABCG2 rs2231142 has a strong effect only in people of Western Polynesian ancestry. Our results emphasize the need to account for sub-population differences when undertaking biomedical genetic research in a group defined by a geographical region and shared ancestry but characterized by migratory events that create bottlenecks and altered genetic structure in the founder populations.

Objective: To examine the role of genetic variation in the renal urate transporter SLC2A9 in gout in New Zealand sample sets of Māori, Pacific Island, and Caucasian ancestry and to determine if the Māori and Pacific Island samples could be useful for fine-mapping., Methods: Patients (n= 56 Māori, 69 Pacific Island, and 131 Caucasian) were recruited from rheumatology outpatient clinics and satisfied the American College of Rheumatology criteria for gout. The control samples comprised 125 Māori subjects, 41 Pacific Island subjects, and 568 Caucasian subjects without arthritis. SLC2A9 single-nucleotide polymorphisms rs16890979 (V253I), rs5028843, rs11942223, and rs12510549 were genotyped (possible etiologic variants in Caucasians)., Results: Association of the major allele of rs16890979, rs11942223, and rs5028843 with gout was observed in all sample sets (P = 3.7 x 10(-7), 1.6 x 10(-6), and 7.6 x 10(-5) for rs11942223 in the Māori, Pacific Island, and Caucasian samples, respectively). One 4-marker haplotype (1/1/2/1; more prevalent in the Māori and Pacific Island control samples) was not observed in a single gout case., Conclusion: Our data confirm a role of SLC2A9 in gout susceptibility in a New Zealand Caucasian sample set, with the effect on risk (odds ratio >2.0) greater than previous estimates. We also demonstrate association of SLC2A9 with gout in samples of Māori and Pacific Island ancestry and a consistent pattern of haplotype association. The presence of both alleles of rs16890979 on susceptibility and protective haplotypes in the Māori and Pacific Island sample is evidence against a role for this nonsynonymous variant as the sole etiologic agent. More extensive linkage disequilibrium in Māori and Pacific Island samples suggests that Caucasian samples may be more useful for fine-mapping.

Objective: To estimate the incidence of and examine risk factors for the development of gout in black and white male physicians., Methods: Data from 2 cohorts of former medical students, 352 black men in the Meharry Cohort Study and 571 white men in the Johns Hopkins Precursors Study, were analyzed. Cases of gout were identified by self-report. Baseline variables and incident hypertension were examined as risk factors for the development of gout in both cohorts., Results: The incidence of gout was 3.11 and 1.82 per 1,000 person-years in the black men and the white men, respectively (P < 0.05); the cumulative incidence was 10.9% and 5.8%, respectively (P = 0.04). The relative risk (RR) for gout among the black men was 1.69 (95% confidence interval [95% CI] 1.02-2.80). This excess risk persisted after adjustment for baseline systolic blood pressure (adjusted RR = 1.96 [95% CI 1.14-3.38]). Incident hypertension was independently associated with the development of gout in univariate analysis (RR = 3.78 [95% CI 2.18-6.58]); when this variable was included as a time-dependent covariate in a Cox model, the excess risk for gout in black men was reduced and no longer significant (adjusted RR = 1.30 [95% CI 0.77-2.19])., Conclusion: The approximately 2-fold excess risk for gout among black men is explained, in part, by a greater risk of incident hypertension.