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高尿酸血症和痛风的遗传学研究进展

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  • 江西农业大学,省部共建猪遗传改良与养殖技术国家重点实验室,南昌 330045
郑敏,硕士研究生,专业方向:动物遗传育种与繁殖。E-mail: wuzhizhengmin@163.com

收稿日期: 2015-09-10

  修回日期: 2015-11-25

  网络出版日期: 2016-04-20

基金资助

国家自然科学基金重点项目(编号:31230069)和江西省青年科学家培养对象项目(编号:20133BCB23013)资助[Supported by the State Key Program of National Natural Science of China (No; 31230069) and Young Scientist Training Project of Jiangxi Province (No; 20133BCB23013)]

Research progress in the genetics of hyperuricaemia and gout

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  • National Key Laboratory for Swine Genetics, Breeding and Production Technology, Jiangxi Agricultural University, Nanchang 330045, China

Received date: 2015-09-10

  Revised date: 2015-11-25

  Online published: 2016-04-20

摘要

痛风是由高尿酸血症引发的一种常见炎性关节炎,受遗传因素和环境因素共同作用。早期研究表明,PRPS1HPRT1等单基因稀有突变会引起嘌呤合成代谢紊乱,从而引发高尿酸血症和痛风。近年来,全基因组关联分析(Genome-wide association studies,GWAS)已检出多个导致高尿酸血症和痛风的易感位点及相关候选基因。其中SLC2A9SLC22A11SLC22A12基因功能缺失性突变可引起遗传性低尿酸血症,而过表达则会加强尿酸的重吸收。ABCG2SLC17A1SLC17A3基因功能缺陷型变异会降低肾脏和肠道对尿酸的排泄量。因此,诱发尿酸排泄障碍(高重吸收和低排泄)的基因变异是影响高尿酸血症和痛风的主要遗传因素。另外,抑制-激活生长因子系统、转录因子、细胞骨架以及基因和环境的互作等因素也一定程度影响血液尿酸水平。在中国汉族人群中,两个新发现的易感基因RFX3KCNQ1可能造成免疫应答受损和胰岛B细胞功能缺陷,从而直接或间接引起高尿酸酸血症和痛风。本文系统综述了高尿酸血症和痛风的遗传学研究,以促进人们对高尿酸血症和痛风发病机理的理解。

本文引用格式

郑敏, 麻骏武 . 高尿酸血症和痛风的遗传学研究进展[J]. 遗传, 2016 , 38(4) : 300 -313 . DOI: 10.16288/j.yczz.15-385

Abstract

Gout is one of the most common inflammatory arthritis caused by hyperuricaemia, which is affected by both genetic factors and environmental factors. Early researches show that a few of rare monogenic mutations, such as PRPS1 and HPRT1 mutations, lead to abnormal purine anabolism and then cause hyperuricaemia and gout. In recent years, genome-wide association studies (GWAS) have identified dozens of susceptibility loci and/or candidate genes associated with hyperuricemia and gout. Loss-of-function mutations in SLC2A9, SLC22A11, and SLC22A12 cause hereditary hypouricaemia, while their overexpression may increase the reabsorption of uric acid. In contrast, loss-of-function mutations in ABCG2, SLC17A1, and SLC17A3 cause urate underexcretion of renal and intestinal. These variations leading to blood uric acid excretion disorder (excess reabsorption and underexcretion) are the main genetic factors affecting hyperuicemia and gout. Moreover, to some degree, inhibins-activins growth factor system, transcription factors, cytoskeleton and gene-environment interaction can also affect the level of blood uric acid. In addition, two risk genes, RFX3 and KCNQ1, which might impair immune response and lead to functional deficiency of beta cell were recently discovered to influence hyperuiceamia and gout in Han Chinese. This paper systematically reviews genetic studies on hyperuricaemia and gout to improve our understanding of pathogenesis of hyperuricaemia and gout.

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