痛风的相关基因和遗传学基础研究进展

原发性痛风是一种多基因遗传病,基因多态性及环境是影响人群发病的重要因素。随着分子生物学技术的发展,与原发性高尿酸血症和痛风相关的易感基因相继被发现。本文主要简述这些基因及其突变位点对痛风发病的影响,及其与环境风险因素间潜在的相互作用。     

中老年人高尿酸血症和痛风患者尿微量蛋白含量测定的临床意义

中老年人高尿酸血症和痛风患者尿微量蛋白含量测定的临床意义李美珍张小娟余俊文（广东省佛山市中医院肾内科，佛山５２８０００）痛风是一种嘌呤代谢紊乱所致的疾病，高尿酸血症是痛风最重要的生化基础。肾脏是痛风患者最易受损的靶器官之一，有报道〔１〕痛风患者３０％...     

2型糖尿病伴高尿酸血症的病因与治疗新进展

高尿酸血症是嘌呤代谢障碍性疾病,也是与代谢异常综合征和糖尿病密切相关性疾病之一,其主要原因是尿酸生成过多或肾脏排泄减少.高尿酸血症与肥胖症、高脂血症、高血压病、糖尿病、动脉粥样硬化等疾病呈显著正相关.糖尿病肾病、高血压、高胰岛素血症均可因阻碍肾小管排泌钠与尿酸引起血尿酸增高.血钠增高与高血压相关,高胰岛素血症又与肥胖、脂质代谢异常特别是高甘油三酯血症、肥胖及糖代谢异常共现.高尿酸血症除了引起痛风、肾结石与肾病外,还使糖尿病患者大血管并发症及心脑血管终点事件发生率显著增高.     

非布司他与心血管事件

<正>近年来高尿酸血症患者在中国逐渐增多,已成为继高血压、高血脂和糖尿病后的第四高。高尿酸血症可以造成多脏器损害,包括痛风、肾脏损害、冠心病、脑卒中等,逐渐得到重视。长期降尿酸治疗可以控制痛风的发作,但长期降尿酸治疗是否可以降低心脑血管疾病的风险目前并不确定,尚缺乏大规模高质量的临床试验,有必要进一步的研究。非布司他是一种新型选择性黄嘌呤氧化酶抑制剂,自2009年在美国批准上市以来广泛用于痛风及高尿酸血症的治疗。2017年11月15日美国食品药     

高尿酸血症与痛风的防治误区及热点

高尿酸血症与痛风的防治误区,不痛不吃药有些高尿酸血症患者痛风不发作的时候就不服药。实际上,高尿酸血症不仅是引发痛风的根本原因,而且对人体的多个靶器官都有严重危害,可能引发糖尿病、尿毒症和心脑血管疾病。因此,生活方式和饮食调整仍不能有效控制血尿酸浓度时,建议药物干预。     

痛风和高尿酸血症的危险因素

痛风和高尿酸血症的患病率正逐年升高，且随年龄而渐增，一般男性发病高于女性。不同种族高尿酸血症／痛风的患病率也不同，可能与饮食习惯及生活方式有关。大多数高尿酸血症／痛风患者有遗传倾向，主要是由于嘌呤代谢催化酶缺陷使尿酸生成过多所致。此外，代谢综合征症侯群，如糖尿病、冠心病、高血压、肥胖等也与高尿酸血症／痛风有关。     

甲状腺功能减退症与高尿酸血症

甲状腺功能减退症与高尿酸血症或痛风伴发比例高,甲状腺激素可直接作用于肾脏导致尿酸排泄减少,也可通过调节瘦素水平影响肾脏对尿酸排泄,同时高尿酸血症或痛风通过作用于下丘脑-垂体-甲状腺轴,影响甲状腺激素的合成及分泌,高尿酸血症也可刺激瘦素基因表达或减少其清除,从而影响甲状腺激素水平.甲状腺激素水平降低和血尿酸水平升高是代谢综合征的危险因素,胰岛素抵抗是代谢综合征的核心,故胰岛素抵抗可能是联系高尿酸血症与甲状腺功能减退症的关键环节.     

亚甲基四氢叶酸还原酶基因C677T多态性与高尿酸血症相关

采用PCR-RFLP方法检测高尿酸血症患者和正常对照者亚甲基四氢叶酸还原酶(MTHFR)基因C677T多态性,结果显示,山东沿海地区汉族人MTHFR基因C677T多态性与高尿酸血症相关,T等位基因是其危险因素,但与单纯高尿酸血症是否发展为痛风无关。     

高尿酸血症和痛风的遗传学研究进展

随着世界经济飞速发展和人类生活水平的提高 ,原发性高尿酸血症和痛风的患病率逐年升高 ,近年研究发现其流行病学特征存在种族及性别差异 ,且与生活方式及糖、脂等代谢性疾病相关。应用分子遗传学研究方法 ,发现嘌呤代谢过程的关键酶———次黄嘌呤鸟嘌呤磷酸核糖转移酶 (HPRT)、5 磷酸核糖 1 焦磷酸 (PRPP)合成酶(PRS)等基因突变位点繁多 ,故绝大多数原发性高尿酸血症和痛风系多基因遗传病。对代谢综合征相关基因多态性研究发现N5,N1 0 亚甲基四氢叶酸还原酶 (MTHFR)基因C6 77T突变、β3 肾上腺素能受体基因Trp6 4Arg突变与高尿酸血症相关。     

血清尿酸与高尿酸血症相关疾病

尿酸是人体嘌呤碱基分解代谢终产物,经肾脏排泄。体内尿酸生成超过肾脏排泄时血清尿酸会显著升高,造成高尿酸血症。高尿酸血症与痛风、心血管疾病、肿瘤裂解综合征及肾脏疾病的引发或加剧密切相关。本文对血清尿酸的临床意义进行综述。     

New developments in the epidemiology and genetics of gout

The prevalence of gout appears to be rapidly increasing worldwide and is no longer a disorder suffered primarily by over-fed alcohol consumers. Emerging risk factors include longevity, metabolic syndrome, and new classes of pharmacologic agents. In some ethnic populations, no obvious risk factors can explain the high incidence of hyperuricemia and gout, suggesting a genetic liability. Studies to identify genes associated with gout have included families with defects in purine metabolism, as well as families in whom the occurrence of gout is secondary to renal disorders such as juvenile hyperuricemic nephropathy and medullary cystic kidney disease. Case-control studies of isolated aboriginal cohorts suffering from primary gout have revealed several chromosomal loci that may harbor genes that are important to the development and/or progression of gout.     

New developments in the epidemiology and genetics of gout

The prevalence of gout appears to be rapidly increasing worldwide and is no longer a disorder suffered primarily by over-fed alcohol consumers. Emerging risk factors include longevity, metabolic syndrome, and new classes of pharmacologic agents. In some ethnic populations, no obvious risk factors can explain the high incidence of hyperuricemia and gout, suggesting a genetic liability. Studies to identify genes associated with gout have included families with defects in purine metabolism, as well as families in whom the occurrence of gout is secondary to renal disorders such as juvenile hyperuricemic nephropathy and medullary cystic kidney disease. Case-control studies of isolated aboriginal cohorts suffering from primary gout have revealed several chromosomal loci that may harbor genes that are important to the development and/or progression of gout.     

膳食营养与高尿酸血症和痛风的关系

饮食治疗在高尿酸血症及痛风的作用已被研究证实,随着研究的不断深入,传统的低蛋白、低嘌呤治疗观念正逐步被更新.高尿酸血症及痛风患者常合并高血压、心血管疾病等,因此饮食治疗不仅应控制食物种类,还要进行饮食结构的调整,以便在高尿酸血症及痛风得到缓解的同时降低伴发疾病的风险.     

Clinical aspects of monosodium urate monohydrate crystal deposition disease (gout)

Gout is a clinical syndrome with a limited range of manifestations arising as a result of the deposition of crystals of monosodium urate, the final product of purine metabolism in humans. Hyperuricemia is a common chemical aberration that is most often mild and remains asymptomatic. Thus, hyperuricemia should be distinguished from gout, even though urate supersaturation is necessary for the expression of gout. Uric acid overproduction and diminished renal uric acid excretion are the major mechanisms resulting in hyperuricemia, and an understanding of the basis of hyperuricemia in individual gout patients is an important step in determining appropriate treatment and in identifying underlying disorders, offending drugs and toxins, and inherited enzyme defects, all of which can result in hyperuricemia and gout. A scheme is presented for the evaluation of patients with new-onset gout, along with a discussion of the relationships between gout/hyperuricemia and a variety of metabolic disorders that are unusually prevalent in gouty populations.     

Aspiration of the asymptomatic metatarsophalangeal joint in gout patients and hyperuricemic controls

Asymptomatic metatarsophalangeal joints were aspirated in a group of patients with gout, in 2 control groups with hyperuricemia, and in 1 normouricemic control group. Extracellular urate crystals were present in 70% of gout patients, in 1 of 19 patients with asymptomatic hyperuricemia, and in 2 of 9 patients with renal failure and hyperuricemia but no history of joint disease. Crystals were not found in the 10 normouricemic patients who had other types of arthritis. The presence of crystals in the subjects with gout was not correlated with a history of podagra, duration of gout, presence of tophi, or degree of control of hyperuricemia. Though crystals were found on rare occasions in joint fluid of asymptomatic hyperuricemic subjects, the presence of these crystals in asymptomatic joints was more common in subjects with gout.     

Genetics of Hyperuricemia and Gout: Implications for the Present and Future

Gout is the most common inflammatory arthropathy and occurs in the setting of elevated serum urate levels. Gout is also known to be associated with multiple comorbidities including cardiovascular disease and the metabolic syndrome. Recent advances in research have increased our understanding and improved our knowledge of the pathophysiology of gout. Genome-wide association studies have permitted the identification of several new and common genetic factors that contribute to hyperuricemia and gout. Most of these are involved with the renal urate transport system (the uric acid transportasome), generally considered the most influential regulator of serum urate homeostasis. Thus far, SCL22A12, SCL2A9, and GLUT9 have been found to have the greatest variation and most influence on serum urate levels. However, genetics are only a part of the explanation in the development of hyperuricemia and gout. As results have been mixed, the role of known urate influential genes in gout’s associated comorbidities remains unclear. Regardless, GWAS findings have expanded our understanding of the pathophysiology of hyperuricemia and gout, and will likely play a role in the development of future therapies and treatment of this ancient disease.     

Hyperuricemia, gout, and autosomal dominant polycystic kidney disease

The relationship between hyperuricemia, gout, and autosomal dominant polycystic kidney disease (ADPKD) is not widely recognized. In an attempt to further clarify this relationship, the authors have studied 17 patients with ADPKD, 9 controls, 9 patients with proven gout and chronic renal failure, 11 patients with gout and normal renal function, and 11 patients with chronic renal failure. The mean serum uric acid concentration was higher in patients with ADPKD as a group than in controls (8.0 +/- 1.7 mg/dl vs. 6.4 +/- 1.6 mg/dl, p less than .02). Clinical gout was identified in 24% of patients with ADPKD; none of the patients with chronic renal failure of other etiologies had gout. Fractional excretion of uric acid and the activity of the enzyme hypoxanthine guanine phosphoribosyl transferase (HGPRT) were not different among the groups studied. From this study the authors conclude that ADPKD should be included among those diseases associated with hyperuricemia and gout. A partial deficiency in HGPRT or abnormal renal handling of uric acid do not appear to be responsible for the increased incidence of gout in patients with ADPKD.     

Characteristics of chronic gout in Northern Sulawesi, Indonesia

OBJECTIVE: To identify associations and possible risk factors for gout that may contribute to chronic tophaceous gout in rural and urban districts of North Sulawesi, Indonesia. METHODS: A total of 190 patients with chronic gout and 190 age and sex matched controls were selected from 28 community health centers. Potential risk factors including alcohol consumption, food habits, family history, body weight, related medical conditions, drug use, and laboratory investigations were sought. RESULTS: Alcohol consumption and certain food habits were associated with gout. A positive family history of gout and overweight were also significant risk factors. Renal impairment was found in 86.3% of patients and hyperuricemia in 92.1%. In controls, renal impairment and hyperuricemia were 7.4% and 32.6%, respectively. Patients with hypertension and nephrolithiasis were more at risk of having associated gout. There was a significant association between gout, hyperuricemia, hypercholesterolemia, hypertriglyceridemia, and higher levels of creatinine and urea. There was also a significantly lower level of urine uric acid in gout cases compared with controls. Gouty tophi were found in 91% of these cases with chronic gout. The use of diuretics for treating hypertension, continuing excessive alcohol consumption and purine-rich food habits in untreated gout, and hyperuricemia were associated with chronic and tophaceous gout. Urate-lowering drugs were not available in the community health centers. CONCLUSION: Severe tophaceous gout with deformities and disability is found in North Sulawesi. Prominent risk factors include alcohol, obesity, renal impairment, diet, hypertension, and family history. Improved education about gout seems needed. Urate-lowering drugs are not available in community health centers but are needed, especially in rural areas, as studied here.     

Difficult gout and new approaches for control of hyperuricemia in the allopurinol-allergic patient

A major obstacle to the treatment of hyperuricemia in patients allergic to allopurinol is the limited availability of suitable, equally effective, alternative, urate-lowering drugs. Conventional uricosuric drugs, including probenecid and sulfinpyrazone, are recommended for allopurinolintolerant patients with gout and “underexcretion” hyperuricemia who have normal renal function and no history of nephrolithiasis. Therapeutic options in those in whom traditional uricosuric drugs are contraindicated, ineffective, or poorly tolerated include slow oral desensitization to allopurinol and cautious administration of oxipurinol. Allopurinol desensitization is useful particularly in those who have failed other treatment modalities. If available (as in Europe, South Africa, and Japan), benzbromarone may be tried in patients with gout and mild-to-moderate renal insufficiency. Recombinant urate oxidase can be used in the short-term prophylaxis and treatment of chemotherapy-associated hyperuricemia in patients with lymphoproliferative and myeloproliferative disorders. Hyperuricemia and gout occur with increased frequency in cyclosporine-treated allograft transplant recipients. The management of gout in these patients is complicated by two main factors: cyclosporine-induced renal impairment, and interactions with medications used to preserve the allograft.     

Hyperuricemia and gout

Gout is not a new disease for clinicians; nevertheless, there are still many secrets awaiting discovery for improving knowledge with respect to uric acid metabolism and monosodium urate crystal-induced inflammation. This review of the literature will focus on new insights on the pathogenesis of idiopathic hyperuricemia, and on secondary hyperuricemia and gout. There are also important advances on the pathophysiology of acute gout, especially as a self-limited process (switch from monocyte to macrophage, peroxisome proliferator activated receptor-gamma, and nitric oxide), but also of chronic gouty arthropathy. Armaments for treating hyperuricemia and gout may be already improved by losartan or fenofibrate and, in the future, by urate oxydase-polyethylene glycol 20 and renal handling regulatory molecules. Finally, control of hyperuricemia may also be considered in the prevention and treatment of cardiovascular disease.