Urate testing in gout: why, when and how.

Urate is a frequently measured blood test in people with gout and those at risk of gout. Although gout is potentially curable with long-term urate lowering therapy, confusion about the details of urate measurement has contributed to suboptimal care. In this article, we provide recommendations regarding urate testing in gout, focusing on the use of this test in clinical practice.

Impact of bariatric surgery on serum urate targets in people with morbid obesity and diabetes: a prospective longitudinal study.

OBJECTIVES: Weight loss leads to reduced serum urate (SU) in people with obesity. However, the clinical relevance of such reductions in SU is unknown. This study examined the impact of non-surgical weight loss and bariatric surgery on SU targets in people with morbid obesity and diabetes. METHODS: The study was a single-centre, prospective study of 60 people with type 2 diabetes and body mass index ≥35 kg/m(2). Following 6 months of non-surgical weight loss, all participants had laparoscopic sleeve gastrectomy, with a further 1 year of follow-up. Serial SUs were measured throughout the study. RESULTS: Participants experienced mean (SD) weight loss of 5.5 (4.1) kg prior to surgery and 34.3 (11.1) kg following surgery. SU did not change following non-surgical weight loss (0.38 (0.09) mmol/L at baseline and 0.38 (0.10) mmol/L at follow-up), but increased to 0.44 (0.15) mmol/L in the immediate postoperative period and reduced to 0.30 (0.08) mmol/L 1 year after surgery (p<0.05 for both compared with baseline). Baseline SU, cessation of diuretics, female sex and change in creatinine independently predicted change in SU at the final visit. In participants without gout, SU above saturation levels (≥0.41 mmol/L) were present in 19/48 (40%) at baseline and 1/48 (2%) 1 year after surgery (p<0.0001). In participants with gout, SU above therapeutic target levels (≥0.36 mmol/L) were present in 10/12 (83%) at baseline and 4/12 (33%) 1 year after surgery (p=0.031). CONCLUSIONS: Clinically relevant reductions in SU occur following bariatric surgery in people with diabetes and WHO class II or higher obesity.

Efficacy and tolerability of probenecid as urate-lowering therapy in gout; clinical experience in high-prevalence population.

OBJECTIVE: Probenecid is recommended as urate-lowering therapy (ULT) in patients with gout where xanthine oxidase inhibitors are ineffective, not tolerated, or contraindicated. The aim of our study was to determine the efficacy of probenecid to achieve serum urate (SU) targets (< 0.36 mmol/l) in clinical practice. METHODS: We identified 57 patients prescribed with probenecid from a database of 521 rheumatology clinic attenders with gout. Demographic characteristics, indications for probenecid, probenecid doses, side effects, and laboratory data including estimated glomerular filtration rate (eGFR) and SU were recorded. RESULTS: There were 30/57 (53%) patients treated with probenecid as monotherapy and 27/57 (47%) patients treated with probenecid in combination with allopurinol. Target SU concentrations (< 0.36 mmol/l) were achieved in 10/30 (33%) of the probenecid monotherapy group and 10/27 (37%) of the combination treatment group. Baseline SU concentrations, but not eGFR or probenecid dose, independently predicted achievement of target SU. Target SU was achieved in 5/15 (33%) patients with eGFR < 50 ml/min/1.73 m(2). There was no difference in the percentage of patients achieving SU target in those with eGFR < 50 ml/min/1.73 m(2) compared with those with eGFR ≥ 50 ml/min/1.73 m(2). Adverse events attributed to probenecid were observed in 8/42 (19%) patients with eGFR ≥ 50 ml/min/1.73 m(2) and in 2/15 (13%) patients with eGFR < 50 ml/min/1.73 m(2). CONCLUSION: Probenecid has moderate efficacy as ULT in clinical management of patients with complex gout who have a lack of efficacy or intolerance to allopurinol. Patients with chronic kidney disease may respond to probenecid with similar rates of adverse events.

A new podiatry service for patients with arthritis.

AIM: The aims of this study were to identify the impact of a new podiatric rheumatology service on reducing foot pain, impairment and disability in patients with foot problems associated with rheumatic disease, and to report on patient satisfaction with the service. METHOD: A retrospective study of 245 patients with rheumatic disease at Counties Manukau DHB was conducted. Foot pain, impairment and disability were measured using a self-reporting patient outcome measure, the Foot Function Index. A range of podiatric interventions were reported. A self-administered, postal patient satisfaction questionnaire was sent to 148 patients. RESULTS: Over two-thirds of patients were observed with hallux valgus (bunions). The results demonstrate a significant reduction in foot pain (p<0.001) from initial visit to second visit (18% reduction in pain). A significant decrease in foot disability (p=0.04) was found from initial visit to second visit. No significant differences were seen with foot impairment (p=0.78). A variety of intervention measures were used with 24% of patients being prescribed foot orthoses and 28% of patients given footwear advice. The patient satisfaction survey found 84% of patients reported they were satisfied with the new service and 80% of patients reported that the service helped with their foot problems. CONCLUSION: The current service meets the needs of patients who suffer from rheumatological foot conditions such as rheumatoid arthritis and gout. The need for good foot education, provision of foot orthoses and advice on footwear are crucial to reduce the burden on patients with rheumatological foot conditions.

Inflammatory myopathies--a review of newly diagnosed patients (2004-2008) in the Counties Manukau region.

AIMS: To estimate incidence, review clinical characteristics and management of newly diagnosed patients with idiopathic inflammatory myositis in Counties Manukau and to compare the findings with other reported series in New Zealand and overseas. METHODS: A case note study of computer generated data of patients having a diagnosis of inflammatory myopathy from January 2004 to December 2008 were included in this retrospective review. RESULTS: Twelve patients were newly diagnosed in the 5-year period. Polymyositis (PM) was diagnosed in 58%, dermatomyositis (DM) in 33% and inclusion body myositis (IBM) in 8%. Amyopathic dermatomyositis (ADM) and malignancy associated dermatomyositis were diagnosed in one patient each. There was slight preponderance of men in dermatomyositis and women in polymyositis. Muscle biopsy was performed in 75% and electromyography was reported in 58%. High-dose prednisone was administered to 83%, and 50 % required other immunosuppressives, such as methotrexate (33%) and azathioprine (16%). Overall therapeutic response was good (75%) with 2 deaths (17%), one each in dermatomyositis and polymyositis. Regular follow-up was maintained in 92 %. Nasopharyngeal carcinoma was diagnosed in a patient with polymositis during follow up. CONCLUSIONS: Idiopathic inflammatory myositis is a challenging group of heterogenous disorders. This study highlights the need to review current criteria to include subcategories, such as amyopathic dermatomyositis, and the importance of long term surveillance to detect occult malignancy.

Potential unmet need for gout diagnosis and treatment: capture-recapture analysis of a national administrative dataset.

OBJECTIVE: To estimate the degree of undercount of people diagnosed with gout in administrative datasets using capture-recapture methods. METHODS: Hospitalization and drug dispensing claims (allopurinol or colchicine) data for all Aotearoa New Zealand were used to estimate the prevalence of gout in 2009 (n = 4 295 296). As a comparison, we calculated gout prevalence using a large primary care dataset using general practitioner diagnosis and prescribing records (n = 555 313). For each of these datasets, we estimated the undercount through capture-recapture analysis using a Poisson regression model. A two-list model was used, which included covariates such as age, gender, ethnic groups and New Zealand deprivation quintiles. RESULTS: The crude prevalence of diagnosed gout in the Aotearoa New Zealand population aged ≥ 20 years was 3.75%. The covariate-adjusted capture-recapture estimate of those not recorded but likely to have gout was 0.92%, giving an overall estimated prevalence of 4.67% (95% CI 4.49, 4.90%) for the population aged ≥ 20 years. This amounts to 80% of people with gout being identified by the algorithm for the Aotearoa New Zealand data-that is being recorded in either lists of dispensing of allopurinol or colchicine or hospital discharge. After capture-recapture, gout prevalence for all males aged ≥ 20 years was 7.3% and in older (≥ 65 years) Maori and Pacific men was >30%. CONCLUSION: Capture-recapture analysis of administrative datasets provides a readily available method for estimating an aspect of unmet need in the population-in this instance potentially 20% of those with gout not being identified and treated specifically for this condition.

The renal urate transporter SLC17A1 locus: confirmation of association with gout.

INTRODUCTION: Two major gout-causing genes have been identified, the urate transport genes SLC2A9 and ABCG2. Variation within the SLC17A1 locus, which encodes sodium-dependent phosphate transporter 1, a renal transporter of uric acid, has also been associated with serum urate concentration. However, evidence for association with gout is equivocal. We investigated the association of the SLC17A1 locus with gout in New Zealand sample sets. METHODS: Five variants (rs1165196, rs1183201, rs9358890, rs3799344, rs12664474) were genotyped across a New Zealand sample set totaling 971 cases and 1,742 controls. Cases were ascertained according to American Rheumatism Association criteria. Two population groups were studied: Caucasian and Polynesian. RESULTS: At rs1183201 (SLC17A1), evidence for association with gout was observed in both the Caucasian (odds ratio (OR) = 0.67, P = 3.0 × 10-6) and Polynesian (OR = 0.74, P = 3.0 × 10-3) groups. Meta-analysis confirmed association of rs1183201 with gout at a genome-wide level of significance (OR = 0.70, P = 3.0 × 10-8). Haplotype analysis suggested the presence of a common protective haplotype. CONCLUSION: We confirm the SLC17A1 locus as the third associated with gout at a genome-wide level of significance.

National prevalence of gout derived from administrative health data in Aotearoa New Zealand.

OBJECTIVE: Previous small studies in Aotearoa New Zealand have indicated a high prevalence of gout. This study sought to determine the prevalence of gout in the entire Aotearoa New Zealand population using national-level health data sets. METHODS: We used hospitalization and drug dispensing claims for allopurinol and colchicine for the entire Aotearoa New Zealand population from the Aotearoa New Zealand Health Tracker (ANZHT) to estimate the prevalence of gout in 2009, stratified by age, gender, ethnicity and socio-economic status (n = 4 295 296). RESULTS: were compared with those obtained from an independent large primary care data set (HealthStat, n = 555 313). Results. The all-ages crude prevalence of diagnosed gout in the ANZHT population was 2.69%. A similar prevalence of 2.89% was observed in the HealthStat population standardized to the ANZHT population for age, gender, ethnicity and deprivation. Analysis of the ANZHT population showed that gout was more common in Maori and Pacific people [relative risk (RR) 3.11 and 3.59, respectively], in males (RR 3.58), in those living in the most socio-economically deprived areas (RR 1.41) and in those aged >65 years (RR >40) (P-value for all <0.0001). The prevalence of gout in elderly Maori and Pacific men was particularly high at >25%. CONCLUSION: Applying algorithms to national administrative data sets provides a readily available method for estimating the prevalence of a chronic condition such as gout, where diagnosis and drug treatment are relatively specific for this disease. We have demonstrated high gout prevalence in the entire Aotearoa New Zealand population, particularly among Maori and Pacific people.

The SLC2A9 nonsynonymous Arg265His variant and gout: evidence for a population-specific effect on severity.

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) Maori, Pacific Island and Caucasian samples. METHODS: Rs3733591 was genotyped across gout patients (n = 229, 232 and 327 NZ Maori, Pacific Island and Caucasian samples, respectively) and non-gout controls (n = 343, 174 and 638 Maori, 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 Maori (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 Maori 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.

The combined impact of CYP2C19 and CYP2B6 pharmacogenetics on cyclophosphamide bioactivation.

AIMS: The role of CYP pharmacogenetics in the bioactivation of cyclophosphamide is still controversial. Recent clinical studies have suggested a role for either CYP2C19 or CYP2B6. The aim of this study was to clarify the role of these pharmacogenes. METHODS: We used a combined in vitro-in vivo approach to determine the role of these pharmacogenes in the bioactivation of the prodrug to 4-hydroxy cyclophosphamide (4-OHCP). Cyclophosphamide metabolism was determined in a human liver biobank (n= 14) and in patients receiving the drug for treatment of lupus nephritis (n= 16) RESULTS: In livers of known CYP2C19 and CYP2B6 genotype and protein expression we observed that there was a combined role for both CYP2C19 and CYP2B6 in the bioactivation of cyclophosphamide in vitro. The presence of at least one loss of function (LoF) allele at either CYP2C19 or CYP2B6 resulted in a significant decrease in both V(max) (P= 0.028) and CL(int) (P= 0.0017) compared with livers with no LoF alleles. This dual genotype relationship was also observed in a preliminary clinical study, with patients who had ≥1 LoF allele at either CYP2C19 or CYP2B6 also displaying significantly (P= 0.0316) lower bioactivation of cyclophosphamide. The mean 4-OHCP : CP bioactivation ratio was 0.0014 (95% CI 0.0007, 0.002) compared with 0.0071 (95% CI 0.0001, 0.014) in patients with no LoF alleles at either of these genes. CONCLUSIONS: The presence of ≥1 LoF allele(s) at either CYP2B6 or CYP2C19 appeared to result in decreased bioactivation of cyclophosphamide both in vitro and in patients. Further clinical studies to confirm this relationship are warranted.

The PTPN22 locus and rheumatoid arthritis: no evidence for an effect on risk independent of Arg620Trp.

OBJECTIVES: The Trp(620) allotype of PTPN22 confers susceptibility to rheumatoid arthritis (RA) and certain other classical autoimmune diseases. There has been a report of other variants within the PTPN22 locus that alter risk of RA; protective haplotype '5', haplotype group '6-10' and susceptibility haplotype '4', suggesting the possibility of other PTPN22 variants involved in the pathogenesis of RA independent of R620W (rs2476601). Our aim was to further investigate this possibility. METHODS: A total of 4,460 RA cases and 4,481 controls, all European, were analysed. Single nucleotide polymorphisms rs3789607, rs12144309, rs3811021 and rs12566340 were genotyped over New Zealand (NZ) and UK samples. Publically-available Wellcome Trust Case Control Consortium (WTCCC) genotype data were used. RESULTS: The protective effect of haplotype 5 was confirmed (rs3789607; (OR = 0.91, P = 0.016), and a second protective effect (possibly of haplotype 6) was observed (rs12144309; OR = 0.90, P = 0.021). The previously reported susceptibility effect of haplotype 4 was not replicated; instead a protective effect was observed (rs3811021; OR = 0.85, P = 1.4×10(-5)). Haplotypes defined by rs3789607, rs12144309 and rs3811021 coalesced with the major allele of rs12566340 within the adjacent BFK (B-cell lymphoma 2 (BCL2) family kin) gene. We, therefore, tested rs12566340 for association with RA conditional on rs2476601; there was no evidence for an independent effect at rs12566340 (P = 0.76). Similarly, there was no evidence for an independent effect at rs12566340 in type 1 diabetes (P = 0.85). CONCLUSIONS: We have no evidence for a common variant additional to rs2476601 within the PTPN22 locus that influences the risk of RA. Arg620Trp is almost certainly the single common causal variant.

Outcome of patients on azathioprine: a need for a better pre-treatment assessment and dosing guideline.

BACKGROUND: Azathioprine (AZA) is a commonly used drug for the management of various rheumatologic disorders. Due to individual variation of the metabolism of AZA, related to genetic polymorphism of the thiopurine methyl transferase (TPMT), serious toxic effects can result if inappropriate dose is administered. AZA dosing according to patients TPMT status can reduce drug-induced morbidity and can be cost effective. AIM: To determine the current local practice of AZA dosing, identify AZA-related toxicity and to compare the local practice with the British Society of Rheumatology (BSR) recommendations. METHODS: Retrospective review of patients on AZA for various rheumatologic conditions from inpatient (n=22) and outpatient (n=38) database at Middlemore Hospital, from January 2003 to January 2007. Data were collected on patient's demographics, treatment history including AZA dosing regimen, TPMT testing, drug-related toxicities and their management. RESULTS: The mean age was 53 years; 73% were females. 43% of European ethnicity; mean weight of patient was 75±25 kg. 42% had SLE, 22% had rheumatoid arthritis, and 13% had systemic vasculitis. Average initial dose of AZA prescribed was 100±37 mg. 45% developed AZA related toxicity. AZA was withdrawn in 35 % of patients due to drug-related side-effects and inefficacy.15% of the patients required dose reduction. TPMT status was tested in 6 (10%) patients; three had low TMPT level, needing dose reduction. BSR recommendation for AZA dosing was followed in 15% cases. CONCLUSION: A significant proportion of the studied cohort of rheumatologic patients on AZA had drug-related toxicity resulting in discontinuation of AZA. Our data suggests that better pre-treatment assessment including TPMT testing and the practice of guideline based dosing regimen would reduce the incidence of undue side-effects and discontinuation of such treatment.

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.

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 Maori, Pacific Island and Caucasian samples. Patients (n = 185, 173 and 214, for Maori, 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 Maori samples (OR = 1.08, P(STRAT)= 0.70), with heterogeneity in association evident between the Maori 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 (Maori, 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 Maori 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.

Only one independent genetic association with rheumatoid arthritis within the KIAA1109-TENR-IL2-IL21 locus in Caucasian sample sets: confirmation of association of rs6822844 with rheumatoid arthritis at a genome-wide level of significance.

INTRODUCTION: The single nucleotide polymorphism (SNP) rs6822844 within the KIAA1109-TENR-IL2-IL21 gene cluster has been associated with rheumatoid arthritis (RA). Other variants within this cluster, including rs17388568 that is not in linkage disequilibrium (LD) with rs6822844, and rs907715 that is in moderate LD with rs6822844 and rs17388568, have been associated with a number of autoimmune phenotypes, including type 1 diabetes (T1D). Here we aimed to: one, confirm at a genome-wide level of significance association of rs6822844 with RA and, two, evaluate whether or not there were effects independent of rs6822844 on RA at the KIAA1109-TENR-IL2-IL21 locus. METHODS: A total of 842 Australasian RA patients and 1,115 controls of European Caucasian ancestry were genotyped for rs6822844, rs17388568 and rs907715. Meta-analysis of these data with published and publicly-available data was conducted using STATA. RESULTS: No statistically significant evidence for association was observed in the Australasian sample set for rs6822844 (odds ratio (OR)=0.95 (0.80 to 1.12), P=0.54), or rs17388568 (OR=1.03 (0.90 to 1.19), P=0.65) or rs907715 (OR=0.98 (0.86 to 1.12), P=0.69). When combined in a meta-analysis using data from a total of 9,772 cases and 10,909 controls there was a genome-wide level of significance supporting association of rs6822844 with RA (OR=0.86 (0.82 to 0.91), P=8.8x10(-8), P=2.1x10(-8) including North American Rheumatoid Arthritis Consortium data). Meta-analysis of rs17388568, using a total of 6,585 cases and 7,528 controls, revealed no significant association with RA (OR=1.03, (0.98 to 1.09); P=0.22) and meta-analysis of rs907715 using a total of 2,689 cases and 4,045 controls revealed a trend towards association (OR=0.93 (0.87 to 1.00), P=0.07). However, this trend was not independent of the association at rs6822844. CONCLUSIONS: The KIAA1109-TENR-IL2-IL21 gene cluster, that encodes an interleukin (IL-21) that plays an important role in Th17 cell biology, is the 20th locus for which there is a genome-wide (P

Association of variation in Fcgamma receptor 3B gene copy number with rheumatoid arthritis in Caucasian samples.

OBJECTIVE: There is increasing evidence that variation in gene copy number (CN) influences clinical phenotype. The low-affinity Fcgamma receptor 3B (FCGR3B) located in the FCGR gene cluster is a CN polymorphic gene involved in the recruitment to sites of inflammation and activation of polymorphonuclear neutrophils (PMNs). Given recent evidence that low FCGR3B CN is a risk factor for systemic but not organ-specific autoimmune disease and the potential importance of PMN in the pathophysiology of rheumatoid arthritis (RA), the authors hypothesised that FCGR3B gene dosage influences susceptibility to RA. METHODS: FCGR3B CN was measured in 643 cases of RA and 461 controls from New Zealand (NZ), with follow-up analysis in 768 cases and 702 controls from the Netherlands and 250 cases and 211 controls from the UK. All subjects were of Caucasian ancestry. RESULTS: Significant evidence for an association between CN <2 and RA was observed in the Dutch cohort (OR 2.01 (95% CI 1.37 to 2.94), p=3 x 10-4) but not in the two smaller cohorts (OR 1.45 (95% CI 0.92 to 2.26), p=0.11 and OR 1.33 (95% CI 0.58 to 3.02), p=0.50 for the NZ and UK populations, respectively). The association was evident in a meta-analysis which included a previously published Caucasian sample set (OR 1.67 (95% CI 1.28 to 2.17), p=1.2 x 10-4). CONCLUSIONS: One possible mechanism to explain the association between reduced FCGR3B CN and RA is the reduced clearance of immune complex during inflammation. However, it is not known whether the association between RA and FCGR3B CN is aetiological or acts as a proxy marker for another biologically relevant variant. More detailed examination of genetic variation within the FCGR gene cluster is required.

Role of the urate transporter SLC2A9 gene in susceptibility to gout in New Zealand Maori, Pacific Island, and Caucasian case-control sample sets.

OBJECTIVE: To examine the role of genetic variation in the renal urate transporter SLC2A9 in gout in New Zealand sample sets of Maori, Pacific Island, and Caucasian ancestry and to determine if the Maori and Pacific Island samples could be useful for fine-mapping. METHODS: Patients (n= 56 Maori, 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 Maori 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 Maori, Pacific Island, and Caucasian samples, respectively). One 4-marker haplotype (1/1/2/1; more prevalent in the Maori 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 Maori 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 Maori and Pacific Island sample is evidence against a role for this nonsynonymous variant as the sole etiologic agent. More extensive linkage disequilibrium in Maori and Pacific Island samples suggests that Caucasian samples may be more useful for fine-mapping.

Clinical audit of foot problems in patients with rheumatoid arthritis treated at Counties Manukau District Health Board, Auckland, New Zealand.

BACKGROUND: At diagnosis, 16% of rheumatoid arthritis (RA) patients may have foot joint involvement, increasing to 90% as disease duration increases. This can lead to joint instability, difficulties in walking and limitation in functional ability that restricts activities of daily living. The podiatrist plays an important role in the multidisciplinary team approach to the management of foot problems. The aim of this study was to undertake a clinical audit of foot problems in patients with RA treated at Counties Manukau District Health Board. METHODS: Patients with RA were identified through rheumatological clinics run within CMDHB. 100 patients were eligible for inclusion. Specific foot outcome tools were used to evaluate pain, disability and function. Observation on foot lesions were noted and previous history of foot assessment, footwear/insoles and foot surgery were evaluated. RESULTS: The median age of the cohort was 60 (IQR: 51-64) years old with median disease duration of 15 (IQR: 7.3-25) years. Over 85% presented with foot lesions that included corns and callus over the forefoot region and lesser toe deformities. Moderate to high disability was noted. High levels of forefoot structural damage were observed. 76% had not seen a podiatrist and 77% reported no previous formal foot assessment. 40% had been seen at the orthotic centre for specialised footwear and insoles. 27% of RA patients reported previous foot surgery. A large proportion of patients wore inappropriate footwear. CONCLUSION: This clinical audit suggests that the majority of RA patients suffer from foot problems. Future recommendations include the provision of a podiatrist within the current CMDHB multidisciplinary rheumatology team to ensure better services for RA patients with foot problems.