An update on the genetic architecture of hyperuricemia and gout

作者：Merriman Tony R^*

来源：Arthritis Research and Therapy, 2015, 17(1): 98.

DOI：10.1186/s13075-015-0609-2

Genome-wide association studies that scan the genome for common genetic variants associated with phenotype have greatly advanced medical knowledge. Hyperuricemia is no exception, with 28 loci identified. However, genetic control of pathways determining gout in the presence of hyperuricemia is still poorly understood. Two important pathways determining hyperuricemia have been confirmed (renal and gut excretion of uric acid with glycolysis now firmly implicated). Major urate loci are SLC2A9 and ABCG2. Recent studies show that SLC2A9 is involved in renal and gut excretion of uric acid and is implicated in antioxidant defense. Although etiological variants at SLC2A9 are yet to be identified, it is clear that considerable genetic complexity exists at the SLC2A9 locus, with multiple statistically independent genetic variants and local epistatic interactions. The positions of implicated genetic variants within or near chromatin regions involved in transcriptional control suggest that this mechanism (rather than structural changes of genetic association data with expression data. As expected, the urate loci associate with gout, although inconsistent asymptomatic hyperurcemic controls would be expected to increase the ability to detect genetic associations with gout.

• 出版日期2015-4-10