原发性高尿酸血症和痛风分子遗传学研究进展

近年来原发性高尿酸血症和痛风的发病率逐年上升,高尿酸血症为痛风的早期阶段,长期高尿酸血症除易诱发痛风外,尚易累及肾脏和心脑血管系统,导致严重的肾脏及心脑血管疾病,但其遗传模式和易感基因尚不清楚。近年来的研究发现,嘌呤代谢过程中关键酶的缺陷及4个尿酸盐转运蛋白基因变异与高尿酸血症和痛风相关。本文对高尿酸血症和痛风的遗传模式、相关的易感基因及其染色体定位进行综述。     

高尿酸血症与痛风患者并发肾结石的影响因素

目的收集高尿酸血症及痛风患者的临床资料及生化结果,分析高尿酸血症及痛风患者并发肾结石的危险因素。方法收集安徽省立医院门诊和住院及体检中心的痛风患者82例及高尿酸血症患者178例进行对照研究,所有患者统一问卷调查,收集一般资料及实验室检查数据,均进行双肾、输尿管、膀胱B超;采用组间对照及二元Logistic回归方法进行统计学分析。结果痛风组与高尿酸血症组肾结石发生率分别为36.6%和27.5%,两组比较差异无统计学差异(P>0.05)。痛风并发肾结石组相比痛风无肾结石组身高更高、体质量更重、病程更长、低密度脂蛋白(LDL)较高(P<0.05)。Logistic回归分析显示:病程>9年[OR=23.493,95%CI(2.824~195.421),P=0.003]、LDL≥4.1 mmol/L[OR=10.160,95%CI(1.218~84.747),P=0.032]是痛风患者发生肾结石的危险因素;痛风并发肾结石组相比高尿酸血症并发肾结石组有吸烟史、饮酒史的比例更高(P<0.05);所有高尿酸血症患者并发结石组相比高尿酸血症无肾结石组的体质量更重,BMI更高,舒张压更高(P<0.05)。结论高尿酸血症与痛风患者均有较高的肾结石发生率。病程>9年、LDL≥4.1 mmol/L是痛风患者肾结石发病的独立危险因素。高体质量及高体质量指数的痛风/高尿酸血症患者更应注意进行泌尿系结石的筛查以利于早期发现肾结石并及时治疗。     

双能CT在诊断痛风心血管损害中的应用价值

痛风是由尿酸钠结晶沉积在关节或其他组织中引起的一种常见的疾病,其发病率和患病率呈逐年上升趋势,高尿酸血症是发展为痛风最重要的危险因素。近年来许多流行病学和实验研究均证实痛风与高血压、冠心病和心肌梗死等心血管疾病的发生和死亡密切相关。而双能CT作为一种新型的无创性影像学检查手段,可以特异性并定量显示尿酸盐结晶,近年来已成为诊断痛风的一个有效工具,有研究发现其在痛风心血管损害的诊断中也有着很好的临床价值。该综述分析痛风与心血管疾病之间复杂的相关性,以及双能CT在诊断痛风心血管损害中的优势和应用价值。     

Influence of intestinal microecology in the development of gout or hyperuricemia and the potential therapeutic targets

Gout and hyperuricemia are common metabolic diseases. Patients with purine metabolism disorder and/or decreased uric acid excretion showed increased uric acid levels in the blood. The increase of uric acid in the blood leads to the deposition of urate crystals in tissues, joints, and kidneys, and causes gout. Recent studies have revealed that imbalance of the intestinal microecology is closely related to the occurrence and development of hyperuricemia and gout. Disorder of the intestinal flora often occurs in patients with gout, and high purine and high fructose may induce the disorder of intestinal flora. Short-chain fatty acids and endotoxins produced by intestinal bacteria are closely related to the inflammatory response of gout. This article summarizes the characteristics of intestinal microecology in patients or animal models with hyperuricemia or gout, and explores the relationship between intestinal microecology and gout or hyperuricemia from the aspect of the intestinal barrier, intestinal microorganisms, intestinal metabolites, and intestinal immune system. We also review the current status of hyperuricemia treatment by targeting intestinal microecology.     

Potential molecular mechanisms of Ermiao san in the treatment of hyperuricemia and gout based on network pharmacology with molecular docking

A network pharmacology integrated molecular docking strategy was used to predict the underlying molecular mechanism of Ermiao san in the treatment of hyperuricemia and gout. Traditional Chinese medicine systems pharmacology (TCMSP) database and analysis platform were used to screen out the active compounds and their targets of Ermiao san. The disease target genes related to hyperuricemia (HUA) and gout were obtained by searching CTD, DisGeNET, DrugBank, GeneCards, OMIM, TTD, and PharmGKB databases with “Hyperuricemia” and “Gout” as keywords, respectively. The potential targets of Ermiao san in the treatment of HUA and gout were screened through a Venn diagram. The protein–protein interaction network was constructed using Cytoscape software. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were then conducted. Finally, some compounds and core targets were selected for molecular docking verification by Autodock Vina and Pymol software. Forty-six active compounds, such as quercetin, wogonin and beta-sitosterol, etc were identified. Ermiao san plays a therapeutic role in HUA and gout regulating various biological processes, cellular compounds, and molecular functions. The core targets of Ermiao san for treating HUA and gout are AT1 (namely Protein Kinase Bα), interleukin-1 beta, prostaglandin-endoperoxide synthase 2, JUN, etc. And the key pathways are nuclear factor-κB, interleukin-17 and tumor necrosis factor. The results of molecular docking analyses suggested that active compounds of Ermiao san could bind well to the core protein receptors. Ermiao san has a synergistic mechanism of multiple compounds, multiple targets, and multiple pathways in the treatment of HUA and gout, which provides a good theoretical basis for the clinical application.     

Dietary factors associated with hyperuricemia in adults

OBJECTIVES: Although diet has long been assumed to be associated with hyperuricemia, the association between diet and hyperuricemia remains to be verified. METHODS: The Nutrition and Health Survey in Taiwan (NAHSIT) implemented between 1993 and 1996 was a nationwide survey using a stratified multistage sampling design. A food frequency questionnaire (FFQ), 24-hour diet recall, and blood samples were utilized. Hyperuricemia was defined as serum urate >7.7 mg/dL for men and >6.6 mg/dL for women. RESULTS: In total, 2176 adults, 987 (45%) men and 1189 (55%) women, were recruited. Mean serum urate was 6.81 +/- 1.66 mg/dL (range, 2.5-16.8 mg/dL) and 5.47 +/- 1.55 mg/dL (range, 1.4-11.5 mg/dL) for men and women, respectively. Multiple logistic regression analysis indicated that beer consumption in both the FFQ and the 24-hour diet recall were significantly associated with hyperuricemia in men after adjusting for age, total caloric intake, body mass index, and geographic area. In FFQ, the adjusted odds ratio was 1.49 for men who imbibed 0.1 to 11.6 g ethanol (<1 standard drink) daily and 1.56 for men who imbibed > or =11.7 g ethanol (> or =1 standard drink) daily, when compared with that for men who did not drink beer (P = 0.035). In the 24-hour diet recall, the adjusted odds ratio for men who drank <5 cans of beer daily was 1.13, and for men who drank > or =5 cans daily was 1.28 when compared with that for men who did not drink beer (P = 0.003). CONCLUSIONS: This cross-sectional survey demonstrated that beer intake is independently associated with increased risk of hyperuricemia in men. Restricted beer intake may help prevent hyperuricemia in the population. The finding of elevated mean serum urate levels over recent decades warrants further study.     

Analysis of urolithiasis in patients with gout and hyperuricemia using ultrasonography

The number of patients with gout and hyperuricemia is increasing in Japan. Urolithiasis is one of the important complications in this disease and early diagnosis of urolithiasis is necessary in disease management. Therefore, we expected to find an exact incidence of urolithiasis in Japanese gouty and hyperuricemic patients in our study. We examined 208 patients using ultrasonography (US) of the abdomen at our hospital (171 primary gout and 37 asymptomatic hyperuricemia). We examined the incidence of urolithiasis in US of the abdomen, past history and urine occult blood reaction in gouty and hyperuricemic patients. We also examined the duration of the current illness. The total number of ‘positive findings’ in US of the abdomen was 64 among 208 cases (30.8%). For these 64 with ‘positive findings’, 51.6% had ‘calcification’ or ‘stone formation’ in bilateral kidneys and 48.4% showed ‘positive findings’ before the onset of gouty arthritis. Among the 208 cases, 16.3% had a history of urolithiasis. Of the 59 cases with ‘stone formation’ among the 64 with ‘positive findings’ in US of the abdomen, 10.2% showed a positive urine occult blood reaction. The frequency of detecting a ‘positive findings’ was evidently proportional to the detection of this illness. In conclusion, the incidence of urolithiasis in gouty and hyperuricemic patients was examined by US of the abdomen. The value of this diagnostic modality was highly appreciated in this instance. The following were suggested as important approaches for the management of gouty or hyperuricemic patients: correction of the serum uric acid levels, early diagnoses of urolithiasis by US of the abdomen, proper alkalization of urine and sufficient diuresis.     

Management of asymptomatic hyperuricemia: Integrated Diabetes & Endocrine Academy (IDEA) consensus statement

AimThe definition and management of asymptomatic hyperuricemia has been an area of controversy for many decades. Debate persists regarding the benefit of treating all cases of asymptomatic hyperuricemia and hence, unsurprisingly there are no clear clinical practice guidelines from our country.ParticipantsTen members consisting of eminent physicians, endocrinologists, nephrologist and a rheumatologist were selected by the Integrated Diabetes & Endocrine Academy (IDEA) for a closed meeting with the aim to come to a consensus.EvidenceA literature search was performed using PubMed and Cochrane library following which published articles in indexed peer review journals were selected.Consensus processEach participant voiced their opinion after reviewing the available data and a consensus was reached after three meetings by voting.ConclusionRecommendations were made on important areas such as definition, investigation and management of asymptomatic hyperuricemia.     

Increasing trend of asymptomatic hyperuricemia under treatment with urate-lowering drugs in Japan

Abstract

Objectives: To describe recent trends in the prevalence of gout and asymptomatic hyperuricemia regarding urate-lowering treatment (ULT) in Japan.

Methods: A database of health insurance claims managed by the Japan Medical Data Center was used to estimate the annual prevalence of gout and asymptomatic hyperuricemia during 2010–2014. ULT was evaluated for status of the two diseases during the same period. The significance of time trends was evaluated by Cochrane–Armitage trend test.

Results: The prevalence of physician-diagnosed gout in men aged 20–64 years was 1.54% (95% CI: 1.49%–1.58%) in 2010, with a slight but significant (p?<?0.001) annual increase, up to 1.66% (95% CI: 1.62%–1.71%) in 2014. In women, gout prevalence was somewhat constant about 0.09% during 2010–2014. Among male patients with gout, 78% received ULT. The prevalence of male patients with asymptomatic hyperuricemia in the same age range, who received ULT, increased significantly from 1.77% (95% CI: 1.72%–1.81%) to 2.14% (95% CI: 2.09%–2.19%) during 2010–2014 (p?<?0.001).

Conclusion: Gout prevalence in adult men in Japan has increased significantly in recent years. The prevalence of asymptomatic hyperuricemia under ULT has also increased significantly and was higher than that of gout.