Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Alabama, United States; Department of Pathology, University of Otago, Dunedin, New Zealand.
Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Alabama, United States; Department of Biochemistry, University of Otago, Dunedin, New Zealand.
Best Pract Res Clin Rheumatol. 2021 Dec;35(4):101721. doi: 10.1016/j.berh.2021.101721. Epub 2021 Nov 1.
This review focuses on the post-genome-wide association study (GWAS) era in gout, i.e., the translation of GWAS genetic association signals into biologically informative knowledge. Analytical and experimental follow-up of individual loci, based on the identification of causal genetic variants, reveals molecular pathogenic pathways. We summarize in detail the largest GWAS in urate to date, then we review follow-up studies and molecular insights from ABCG2, HNF4A, PDZK1, MAF, GCKR, ALDH2, ALDH16A1, SLC22A12, SLC2A9, ABCC4, and SLC22A13, including the role of insulin signaling. One common factor in these pathways is the importance of transcriptional control, including the HNF4α transcription factor. The new molecular knowledge reveals new targets for intervention to manage urate levels and prevent gout.
这篇综述聚焦于痛风的全基因组关联研究（GWAS）后时代，即将 GWAS 遗传关联信号转化为具有生物学意义的知识。基于因果遗传变异的鉴定，对各个基因座进行分析和实验性的后续研究，揭示了分子发病机制。我们详细总结了迄今为止尿酸水平的最大 GWAS，然后我们综述了 ABCG2、HNF4A、PDZK1、MAF、GCKR、ALDH2、ALDH16A1、SLC22A12、SLC2A9、ABCC4 和 SLC22A13 的后续研究和分子见解，包括胰岛素信号的作用。这些途径中的一个共同因素是转录控制的重要性，包括 HNF4α 转录因子。新的分子知识揭示了干预以管理尿酸水平和预防痛风的新靶点。
