Abstract:
Gout is recurrent inflammatory arthritis caused by the deposition of monosodium urate crystals in the joints. The risk factors that predispose to suffering from gout include non-modifiable factors such as gender, age, ethnicity and genetics, and modifiable factors such as diet and lifestyle. It has been shown that the heritability of uric acid levels in the blood is greater than 30%, which indicates that genetics play a key role in these levels. Hyperuricaemia is often a consequence of reduced renal urate excretion since more than 70% is excreted by the kidneys, mainly through the proximal tubule. The mechanisms that explain that hyperuricaemia associated with reduced renal urate excretion is, to a large extent, a proximal renal tubular disorder, have begun to be understood following the identification of two genes that encode the URAT1 and GLUT9 transporters. When they are carriers of loss-of-function mutations, they explain the two known variants of renal tubular hypouricaemia. Some polymorphisms in these genes may have an opposite gain-of-function effect, with a consequent increase in urate reabsorption. Conversely, loss-of-function polymorphisms in other genes that encode transporters involved in urate excretion (ABCG2, ABCC4) can lead to hyperuricaemia. Genome-wide association study (GWAS) methods have made it possible to locate new gout-related loci associated with reduced renal urate excretion (NIPAL1, FAM35A).
摘要:
痛风是由尿酸单钠晶体在关节中沉积引起的复发性炎性关节炎。易患痛风的危险因素包括不可改变的因素,如性别,年龄,种族和遗传学,以及饮食和生活方式等可改变的因素。研究表明,血液中尿酸水平的遗传力大于30%,这表明遗传学在这些水平中起着关键作用。高尿酸血症通常是肾尿酸盐排泄减少的结果,因为超过70%是由肾脏排泄的。主要通过近端小管。解释高尿酸血症与肾尿酸盐排泄减少相关的机制是,在很大程度上,近端肾小管疾病,在鉴定了编码URAT1和GLUT9转运蛋白的两个基因后,已经开始被理解。当它们是功能丧失突变的携带者时,他们解释了肾小管性低尿酸血症的两种已知变种。这些基因中的一些多态性可能具有相反的功能增益效应,从而增加尿酸盐的重吸收。相反,其他编码参与尿酸盐排泄的转运蛋白(ABCG2,ABCC4)基因的功能缺失多态性可导致高尿酸血症。全基因组关联研究(GWAS)方法使定位与肾尿酸排泄减少相关的新痛风相关基因座成为可能(NIPAL1,FAM35A)。