A case-control study of alcohol consumption and drinking behaviour in patients with acute gout.

The alcohol intake and drinking behaviour of 24 patients who presented with acute gout in a family practice over a 5-year period were compared with these features of a control population matched for sex, age, weight and use of hyperuricemia-inducing diuretics. The average weekly alcohol intake of the group with gout was twice that of the control group (p less than 0.02), and a statistically significant relation was found between alcohol abuse and acute gout (p less than 0.05). About half of the patients with gout drank excessively. Acute gout should be considered a possible clinical sign of alcohol abuse.     

An Unusual Patient with Hypothyroidism,Tophaceous Gout,and Marked Joint Destruction

This report describes a 75-year-old Caucasian man with extensive urate deposits and severe gouty arthropathy that confined him to a wheelchair. Since age 50, he suffered multiple acute gout flares and progressive deformities in his hands, feet, knees, and elbows (tophi). Serum creatinine was 1.4 mg/dL and serum urate 9.4 mg/dL. Conditions known to increase uric acid production (psoriasis, chronic bronchitis) and to decrease uric acid excretion (hypothyroidism, metabolic syndrome, and nephroangiosclerosis) may operate in a single patient, illustrating the dramatic clinical course of untreated gout.     

Comorbidities in patients with gout

Gout is one of the most important diseases associated with hyperuricemia. Gout is characterized by acute monoarthritis with frequent flares. Some patients with gout have gouty tophi that are composed of monosodium urate crystals and inflammatory cells. In addition to tophi, gout is associated with various comorbidities such as obesity, hypertension, abnormal lipid metabolism, renal dysfunction, and urolithiasis. We examined the associations of the presence of tophi and comorbidities with demographic and disease characteristic data of gout patients. Subjects were 422 male patients with gout who visited our outpatient clinic. The patients' background data and laboratory data at the first visit were collected from patient records. We investigated the relationship between comorbidities and characteristics of patients using multiple regression models. The age of gout onset was 44 ± 13 years. The duration of gout at the first visit was 6 ± 8 years. Five percent of subjects had tophi. The presence of tophi was significantly associated with the duration of gout and maximum serum uric acid (SUA), indicating a close association of tophi with urate deposition. Reduced estimated glomerular filtration rate was associated with older age of onset, longer duration of gout, and higher levels of maximum SUA, indicating that sustained hyperuricemia relates with renal impairment of gout. Urolithiasis did not associate with gout duration and maximum SUA. The increased frequency of hypertension was associated with the duration of gout, suggesting that poor control of gout is one of the causes of hypertension. This study provides useful information for gout management and patient education.     

An unusual patient with hypothyroidism, tophaceous gout, and marked joint destruction

This report describes a 75-year-old Caucasian man with extensive urate deposits and severe gouty arthropathy that confined him to a wheelchair. Since age 50, he suffered multiple acute gout flares and progressive deformities in his hands, feet, knees, and elbows (tophi). Serum creatinine was 1.4 mg/dL and serum urate 9.4 mg/dL. Conditions known to increase uric acid production (psoriasis, chronic bronchitis) and to decrease uric acid excretion (hypothyroidism, metabolic syndrome, and nephroangiosclerosis) may operate in a single patient, illustrating the dramatic clinical course of untreated gout.     

ABCG2基因rs2231142位点多态性与汉族女性痛风的相关性

目的：ABCG2基因第5外显子区单核苷酸多态性位点rs2231142与中国汉族男性痛风密切相关,基于痛风易感基因存在性别差异的考虑,本研究旨在探讨该单核苷酸多态性位点与中国汉族女性人群痛风易感性之间的相关性。方法：选取185例女性痛风患者和311例女性正常对照者,提取外周血基因组DNA,采用聚合酶链式反应（PCR技术）,特异性扩增ABCG2基因所需要的目的片段并测序,比较痛风组和正常对照组的基因型频率及等位基因频率分布情况。结果：rs2231142位点的CC、CA、AA基因型频率在两组间存在显著差异（x2=16.519,P〈0.001）,且痛风组中A等位基因频率显著高于正常对照组（分别为42.2%和29.3%,P〈0.001,OR 1.76[95%CI：1.35-2.31]）。结论：ABCG2基因第五外显子区rs2231142（C/A）位点的单核苷酸多态性与中国汉族女性人群痛风易感性密切相关,携带A等位基因的汉族女性人群有更高的痛风患病率。ABCG2基因首次被证实为中国汉族女性人群的痛风致病易感基因。     

Soft drinks,fructose consumption,and the risk of gout in men: prospective cohort study

Objective To examine the relation between intake of sugar sweetened soft drinks and fructose and the risk of incident gout in men.Design Prospective cohort over 12 years.Setting Health professionals follow-up study.Participants 46 393 men with no history of gout at baseline who provided information on intake of soft drinks and fructose through validated food frequency questionnaires.Main outcome measure Incident cases of gout meeting the American College of Rheumatology survey criteria for gout.Results During the 12 years of follow-up 755 confirmed incident cases of gout were reported. Increasing intake of sugar sweetened soft drinks was associated with an increasing risk of gout. Compared with consumption of less than one serving of sugar sweetened soft drinks a month the multivariate relative risk of gout for 5-6 servings a week was 1.29 (95% confidence interval 1.00 to 1.68), for one serving a day was 1.45 (1.02 to 2.08), and for two or more servings a day was 1.85 (1.08 to 3.16; P for trend=0.002). Diet soft drinks were not associated with risk of gout (P for trend=0.99). The multivariate relative risk of gout according to increasing fifths of fructose intake were 1.00, 1.29, 1.41, 1.84, and 2.02 (1.49 to 2.75; P for trend <0.001). Other major contributors to fructose intake such as total fruit juice or fructose rich fruits (apples and oranges) were also associated with a higher risk of gout (P values for trend <0.05).Conclusions Prospective data suggest that consumption of sugar sweetened soft drinks and fructose is strongly associated with an increased risk of gout in men. Furthermore, fructose rich fruits and fruit juices may also increase the risk. Diet soft drinks were not associated with the risk of gout.     

Gout and the risk of dementia: a nationwide population-based cohort study

IntroductionUric acid was proposed to have anti-oxidant property and possible neuroprotective effects. We examined the association between gout and dementia with population database.MethodsThe study utilized the claims data from the nationwide representative sample of Taiwan National Health Insurance Research Database (NHIRD). We ascertained patients with gout and dementia covering vascular and non-vascular (including Alzheimer’s) subtypes using International Classification of Diseases Ninth Revision, Clinical Modification (ICD9-CM) codes. A control group matched on sex, age, and index date of gout patients was randomly sampled with a ratio of 1:4 from the same database for comparison.ResultsFrom 2002 to 2008, 28,769 gout patients who were older than 50 years old were identified, and 114,742 control patients was matched into the study. During follow-up, 7,119 patients developed dementia (1,214 with gout, and 5,905 without gout). After adjusting for age, sex, and relevant comorbidities, a Cox regression analysis showed that gout patients had a lower risk of developing non-vascular dementia (hazard ratio (HR): 0.77; 95% confidence interval (CI): 0.72 - 0.83; p < 0.001) and vascular dementia (HR: 0.76; 95% CI: 0.65 - 0.88; p < 0.001).ConclusionsPatients with gout have a lower risk of developing dementia. This phenomenon exists for both non-vascular and vascular types of dementia.     

Risk of end-stage renal disease associated with gout: a nationwide population study

Introduction

We explored the risk of end-stage renal disease (ESRD) among gout patients in a representative cohort in Taiwan.

Methods

The primary database used was the Taiwan National Health Insurance Research Database. Subjects older than 20 years without ESRD, coronary heart disease, or stroke were included in the study. The case definition of gout in the present study was gout diagnosis and medical treatment for gout. An ESRD case was defined by the presence of chronic renal failure necessitating long-term renal replacement therapy. Multivariate Cox proportional hazards models were used to evaluate the risk of ESRD among gout patients.

Results

The analysis included data of 656,108 patients who were followed up for a mean of 8.0 years. Among them, 19,963 (3.0%) patients had gout. At the end of 2008, 2,377 individuals (gout, n = 276; non-gout, n = 2,101) had ESRD, and 861 individuals (gout, n = 77, 27.9%; non-gout, n = 521, 24.8%) died due to ESRD. The rates of incidence of ESRD were 1.73 and 0.41 cases per 1,000 patient-years in the gout and non-gout groups. After adjustment for age, sex, and history of diabetes mellitus and/or hypertension, gout was associated with a hazard ratio (HR) of 1.57 for ESRD (95% confidence interval [CI], 1.38-1.79; P < 0.001). In patients with ESRD, the adjusted HR for death in patients with gout was 0.95 (0.74-1.23, P = 0.71), which was similar to the HR obtained in patients without gout.

Conclusions

Gout is associated with an increased hazard for development of ESRD.     

Bidirectional Association between Self-Reported Hypertension and Gout: The Singapore Chinese Health Study

It has been hypothesized that the association between hypertension and gout is bidirectional, however, few studies have examined this in a prospective cohort. We analyzed data from the Singapore Chinese Health Study (SCHS) follow-up I (1999–2004) and II (2006–2010) interviews, when both physician-diagnosed hypertension and gout were self-reported. We included participants with data for both follow-up interviews and who were free of heart disease, stroke and cancer at follow-up I. The analysis of hypertension and risk of gout included 31,137 participants when prevalent gout cases were excluded, while the analysis of gout and risk of hypertension included 20,369 participants when prevalent hypertension cases were excluded. Cox proportional hazards models were used to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). The mean age at follow-up I was 60.1 (SD 7.3) years, and the average follow-up was 6.8 (SD 1.4) years. In the analysis of hypertension and risk of gout, 682 incident cases were identified. Compared to normotensive participants, hypertensive patients had an88% increased risk of developing gout (HR 1.88; 95% CI 1.61–2.21). In the parallel analysis, 5,450 participants reported to have newly diagnosed hypertension during follow-up. Compared to participants without gout, those with gout had an18% increased risk of developing hypertension (HR 1.18; 95% CI 1.02–1.37). The bidirectional association was stronger in normal weight adults compared to overweight/obese individuals (P _interaction = 0.06 and 0.04, respectively). The hypertension to gout association was stronger in women compared to men (P _interaction = 0.04), while the gout to hypertension association was evident in women but not in men (P _interaction = 0.02). In conclusion, our results suggest that the hypertension-gout association is bidirectional in this cohort of Singapore Chinese adults. The potential interactions of the bidirectional association with obesity and sex deserve further investigations.     

Autopsing history: The mummy of Charlemagne (c. 747 – 814 AD), father of Europe

In this article, a complete history of Charlemagne’s mortal remains is outlined, including the first publication reporting on the most recent tomb opening in 1988. Besides exclusive bioarchaeological details – namely that his body was indeed mummified - a full clinical interpretation of the Emperor’s final illnesses and death is given: a likely combination of osteoarthritis, gout and a recurrent fever caused by an infectious disease.     

A pilot study of IL-1 inhibition by anakinra in acute gout

Monosodium urate crystals stimulate monocytes and macrophages to release IL-1β through the NALP3 component of the inflammasome. The effectiveness of IL-1 inhibition in hereditary autoinflammatory syndromes with mutations in the NALP3 protein suggested that IL-1 inhibition might also be effective in relieving the inflammatory manifestations of acute gout. The effectiveness of IL-1 inhibition was first evaluated in a mouse model of monosodium urate crystal-induced inflammation. IL-1 inhibition prevented peritoneal neutrophil accumulation but TNF blockade had no effect. Based on these findings, we performed a pilot, open-labeled study (trial registration number ISRCTN10862635) in 10 patients with gout who could not tolerate or had failed standard antiinflammatory therapies. All patients received 100 mg anakinra daily for 3 days. All 10 patients with acute gout responded rapidly to anakinra. No adverse effects were observed. IL-1 blockade appears to be an effective therapy for acute gouty arthritis. The clinical findings need to be confirmed in a controlled study.     

Characteristic dysbiosis in gout and the impact of a uric acid-lowering treatment,febuxostat on the gut microbiota

Gut dysbiosis is suggested to play a critical role in the pathogenesis of gout. The aim of our study was to identify the characteristic dysbiosis of the gut microbiota in gout patients and the impact of a commonly used uric acid-lowering treatment, febuxostat on gut microbiota in gout. 16S ribosomal RNA sequencing and metagenomic shotgun sequencing was performed on fecal DNA isolated from 38 untreated gout patients, 38 gout patients treated with febuxostat, and 26 healthy controls. A restriction of gut microbiota biodiversity was detected in the untreated gout patients, and the alteration was partly restored by febuxostat. Biochemical metabolic indexes involved in liver and kidney metabolism were significantly associated with the gut microbiota composition in gout patients. Functional analysis revealed that the gut microbiome of gout patients had an enriched function on carbohydrate metabolism but a lower potential for purine metabolism, which was comparatively enhanced in the febuxostat treated gout patients. A classification microbial model obtained a high mean area under the curve up to 0.973. Therefore, gut dysbiosis characterizings gout could potentially serve as a noninvasive diagnostic tool for gout and may be a promising target of future preventive interventions.     

A concise history of gout and hyperuricemia and their treatment

First identified by the Egyptians in 2640 BC, podagra (acute gout occurring in the first metatarsophalangeal joint) was later recognized by Hippocrates in the fifth century BC, who referred to it as 'the unwalkable disease'. The term is derived from the Latin word gutta (or 'drop'), and referred to the prevailing medieval belief that an excess of one of the four 'humors'--which in equilibrium were thought to maintain health--would, under certain circumstances, 'drop' or flow into a joint, causing pain and inflammation. Throughout history, gout has been associated with rich foods and excessive alcohol consumption. Because it is clearly associated with a lifestyle that, at least in the past, could only be afforded by the affluent, gout has been referred to as the 'disease of kings'. Although there is evidence that colchicine, an alkaloid derived from the autumn crocus (Colchicum autumnale), was used as a powerful purgative in ancient Greece more than 2000 years ago, its first use as a selective and specific treatment for gout is attributed to the Byzantine Christian physician Alexander of Tralles in the sixth century AD. Uricosuric agents were first used at the end of the 19th century. In the modern era, nonsteroidal anti-inflammatory drugs are usually the drugs of choice for treating acute gout. Perhaps the most important historical advance in the treatment of hyperuricemia was the development of xanthine oxidase inhibitors, which are effective in reducing plasma and urinary urate levels and have been shown to reverse the development of tophaceous deposits.     

A DNA polymorphism of an apoprotein gene associates with the hypertriglyceridaemia of primary gout

Summary Genomic hybridization analysis has been used to investigate allelic frequencies of the genes coding for the four major apoproteins of high density lipoprotein (HDL); apoproteins AI, AII, CII and CIII, in a group of Caucasian subjects with primary gout. An uncommon allelic variant of the apoprotein CIII gene (the S2 allele) was significantly more common among the patients with gout (9/48, 19%) than among normouricaemic controls who were either randomly selected (1/41, 2%, P=0.03) or normotriglyceidaemic (0/33, 0%, P=0.013). Approximately 46% (22/48) of the subjects with gout were hypertriglyceridaemic (with a serum triglyceride >2.1 mmol/l). Of the 22 patients in this subgroup, 5 (23%) had the uncommon S1S2 genotype, which was also a significantly greater proportion than among the normotriglyceridaemic controls (P=0.015). These data suggest that the hypertriglyceridaemia associated with primary gout may have a genetic basis. In contrast, we found no differences in the frequencies of restriction fragment length polymorphisms of the genes for apoproteins AI, AII and CII.     

Visceral fat obesity is highly associated with primary gout in a metabolically obese but normal weighted population: a case control study

IntroductionGout is a chronic inflammatory disease the development of which is associated with obesity-induced metabolic abnormalities. However, a substantial number of non-obese patients (body mass index [BMI] <25 kg/m²) also develop gout in Korea. It was suggested that accumulation of visceral fat rather than subcutaneous fat is associated with metabolic abnormalities and hyperuricemia in patients with gout; therefore, we hypothesized that visceral fat accumulation was increased in non-obese gout patients.MethodsOne hundred and three male patients with primary gout and 204 age-matched healthy controls who attended a health check-up examination were recruited after the review of medical charts. The visceral fat area (VFA) was measured using the bioelectrical impedance analysis (BIA) method, and a VFA >100 cm² was defined as visceral fat obesity (VFO). The frequency of VFO was compared in patients and control groups. The frequencies of metabolic syndrome and related parameters were also investigated.ResultsBMI, waist circumference, total fat mass, serum triglycerides, and serum glucose levels were significantly greater in patients compared with controls. VFA and the prevalence of VFO was increased in gout patients compared with controls. There were positive correlations between VFA and serum triglyceride levels and serum glucose levels. Multivariate regression analysis revealed that VFO is an independent risk factor for gout (odds ratio 2.488, 95% confidence interval 1.041–4.435). In non-obese subgroup analyses (gout patients, n = 38; healthy controls, n = 150), VFA (98.7 ± 19.3 vs. 91.0 ± 16.7, P = 0.016) and the frequency of VFO (47.4 vs. 27.3%, P = 0.017) remained significantly higher in gout patients. There was no difference in either BMI or total fat mass between patients and controls in the non-obese subgroup. The prevalence of metabolic syndrome in patients with gout was 31.7% (33/104), compared with 13.2% (5/38) in the non-obese subgroup according to modified ATP III criteria.ConclusionVFO, measured using BIA, is observed more frequently in patients with primary gout compared with healthy controls, even in non-obese individuals. Therefore, VFO might more properly represent metabolic derangements in patients with gout than general obesity.     

Identification of ABCG2 dysfunction as a major factor contributing to gout

The ATP-binding cassette, subfamily G, member 2 gene ABCG2/BCRP locates in a gout-susceptibility locus (MIM 138900) on chromosome 4q. Recent genome-wide association studies also showed that the ABCG2 gene relates to serum uric acid levels and gout. Since ABCG2 is also known as a transporter of nucleotide analogs that are structurally similar to urate, and is an exporter that has common polymorphic reduced functionality variants, ABCG2 could be a urate secretion transporter and a gene causing gout. To find candidate mutations in ABCG2, we performed a mutation analysis of the ABCG2 gene in 90 Japanese patients with hyperuricemia and found six non-synonymous mutations. Among the variants, ATP-dependent urate transport was reduced or eliminated in five variants, and two out of the five variants (Q126X and Q141K) were frequently detected in patients. Haplotype frequency analysis revealed that there is no simultaneous presence of Q126X and Q141K in one haplotype. As Q126X and Q141K are a nonfunctional and half-functional haplotype, respectively, their genotype combinations are divided into four estimated functional groups. The association study with 161 male gout patients and 865 male controls showed that all of those who had dysfunctional ABCG2 had an increased risk of gout, and that a remarkable risk was observed in those with ≤1/4 function (OR, 25.8; 95% CI, 10.3-64.6; p = 3.39 × 10(-21)). In 2,150 Japanese individuals, the frequency of those with dysfunctional ABCG2 was more than 50%. Our function-based clinicogenetic analysis identified the combinations of dysfunctional variants of ABCG2 as a major contributing factor in Japanese patients with gout.     

高尿酸血症和痛风的流行病学及其危险因素的研究进展

高尿酸血症和痛风是由于长期嘌呤代谢紊乱所引起的一种代谢性疾病,随着各国经济的发展,其患病率在全球范围呈逐年升高的趋势,因此相关研究也日益增多.本文就近年来有关高尿酸血症与痛风的流行病学及其危险因素的研究作一综述,并着重阐述高尿酸血症与糖尿病关系的相关研究进展.     

Identification of ABCG2 Dysfunction as a Major Factor Contributing to Gout

The ATP-binding cassette, subfamily G, member 2 gene ABCG2/BCRP locates in a gout-susceptibility locus (MIM 138900) on chromosome 4q. Recent genome-wide association studies also showed that the ABCG2 gene relates to serum uric acid levels and gout. Since ABCG2 is also known as a transporter of nucleotide analogs that are structurally similar to urate, and is an exporter that has common polymorphic reduced functionality variants, ABCG2 could be a urate secretion transporter and a gene causing gout. To find candidate mutations in ABCG2, we performed a mutation analysis of the ABCG2 gene in 90 Japanese patients with hyperuricemia and found six non-synonymous mutations. Among the variants, ATP-dependent urate transport was reduced or eliminated in five variants, and two out of the five variants (Q126X and Q141K) were frequently detected in patients. Haplotype frequency analysis revealed that there is no simultaneous presence of Q126X and Q141K in one haplotype. As Q126X and Q141K are a nonfunctional and half-functional haplotype, respectively, their genotype combinations are divided into four estimated functional groups. The association study with 161 male gout patients and 865 male controls showed that all of those who had dysfunctional ABCG2 had an increased risk of gout, and that a remarkable risk was observed in those with ≤1/4 function (OR, 25.8; 95% CI, 10.3–64.6; p = 3.39 × 10^?21). In 2,150 Japanese individuals, the frequency of those with dysfunctional ABCG2 was more than 50%. Our function-based clinicogenetic analysis identified the combinations of dysfunctional variants of ABCG2 as a major contributing factor in Japanese patients with gout.     

Association between gout and polymorphisms in GCKR in male Han Chinese

Several genome-wide association studies (GWASs) have reported associations between single nucleotide polymorphisms (SNPs) and uric acid concentrations or gout in a number of different ethnic populations. To clarify the global relevance of the previously identified SNPs in the development of the qualitative trait gout, in the present study, the associations between two SNPs in the glucokinase (hexokinase 4) regulator (GCKR) gene and gout were assessed in a male Chinese Han population. The study population comprised 476 male gout patients and 465 male controls. Multiple PCR was performed using time-of-flight mass spectrometry (MALDI-TOF MS) to identify genotypes. Two SNPs, rs780093 and rs780094, located in intronic regions of the GCKR gene were found to be significantly associated with the development of gout. Thus, the association between the two GCKR SNPs and gout was replicated in the male Han Chinese population investigated in the present study. Furthermore, GCKR was identified as a novel candidate gene associated with gout.