Key Points The majority of the genes that associate with hyperuricaemia and gout in genome-wide association studies have been implicated in the renal urate-transport system Genetic variation explains only a modest level of variance in serum uric acid levels (6%) Serum uric acid levels are determined by the net balance between urate absorption and secretion, which is mediated by separate sets of transporters in the renal proximal tubule The clinical utility of testing for urate-associated genes seems limited because serum urate levels themselves can effectively predict gout risk at a low cost Urate-associated genes and genetically determined urate levels have been largely unassociated with cardiovascular or metabolic outcomes, suggesting that serum uric acid does not have a causal role in these outcomes Strong pharmacogenetic associations between HLA-B * 5801 alleles and severe allopurinol-hypersensitivity reactions have been shown in Asian and European populations, suggesting clinical utility of testing for these alleles This is a preview of subscription content, access via your institution Access options Subscribe to this journal Receive 12 print issues and online access 183,71 per year only 15,31 per issue Buy this article Purchase on SpringerLink Instant access to the full article PDF
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In line with this, mice with an -cell specific knock-down of PC1/3, resulting in significantly reduced islet GLP-1 content, were able to maintain normal glucose tolerance, suggesting that islet GLP-1 may not be essential and/or that it can be compensated for by intestinally derived GLP-1 under normal conditions
Yokote K et al
