The genetics of gout: towards personalised medicine?

Abstract

Over the last decade, there have been major advances in the understanding of the genetic basis of hyperuricaemia and gout as well as of the pharmacogenetics of urate-lowering therapy. Key findings include the reporting of 28 urate-associated loci, the discovery that ABCG2 plays a central role on extra-renal uric acid excretion, the identification of genes associated with development of gout in the context of hyperuricaemia, recognition that ABCG2 variants influence allopurinol response, and the impact of HLA-B*5801 testing in reducing the prevalence of allopurinol hypersensitivity in high-risk populations. These advances, together with the reducing cost of whole genome sequencing, mean that integrated personalised medicine approaches may soon be possible in clinical practice. Genetic data may inform assessment of disease prognosis in individuals with hyperuricaemia or established gout, personalised lifestyle advice, selection and dosing of urate-lowering therapy, and prevention of serious medication adverse effects. In this article, we summarise the discoveries from genome-wide association studies and discuss the potential for translation of these findings into clinical practice.

Risk of incident gout in kidney transplant recipients: A retrospective cohort study

“…Kidney uric acid transporter genes ( SLC2A9 , ABCG2 , SLC22A11 , SLC22A12 , SLC17A1 and the auxiliary molecule PDZK1 ) are responsible for modulating serum uric acid levels. Variations in these genes account for most hyperuricemia and gout . The SLC22A12/URAT1 gene encodes a kidney uric acid reuptake transporter.…”

“…Although kidney transplant recipients are associated with an increased risk of incident gout, there is currently few reports from Taiwan on the incidence of gout in kidney transplant recipients. Importantly, variations in kidney uric acid transporter genes ( SLC2A9 , ABCG2 , SLC22A11 , SLC22A12 , SLC17A1 and the auxiliary molecule PDZK1 ) can be held accountable for most hyperuricemia and gout . DNA damage in kidney transplant patients has been observed .…”

Personalized Medicine of Urate-Lowering Therapy for Gout

“…It is advocated to promote healthy eating and drinking for gout patients, such as reducing intake of beer, sugar-sweetened drinks, and purine-rich foods such as meat, offal and seafood. Increased intake of cherries, omega-3 fatty acids, low fat milk and coffee are also advocated [116]. There was evidence for a non-additive interaction of sugar-sweetened drinks consumption with a urate-associated variant of SLC2A9 for the risk of gout [117] .…”

Abcg2 Gene Polymorphism in Patients With Gout in Zabaikalsky Krai

“…В этой связи особую актуальность приобретает изучение роли генетических факторов в понимании патогенеза ГУ и подагры. В литературе представлены доказательства влияния генетических аспектов в регуляции синтеза и экскреции МК в эксперименте и клинике [10,11]. В полногеномном ассоциативном исследовании, 2015 (GWASs − genome-wide association study) были определены 6 уратных транспортеров, которые влияют на уровень МК сыворотки крови, регулируя процессы реабсорбции и экскреции уратов [10,12].…”