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19-07-2019 | Gout | News

Genetic loci influencing asymptomatic hyperuricemia to gout progression identified

medwireNews: A Japanese genome-wide association study (GWAS) has identified novel genetic loci associated with the susceptibility of gout in individuals with asymptomatic hyperuricemia.

These findings should help to develop “an understanding of why only a proportion of hyperuricaemia cases develop gout,” and “assist physicians to identify, based on individual genetic differences, [asymptomatic hyperuricemia] cases who need individually tailored preemptive medicine for gout,” say the study authors.

They explain that the development of gout involves two steps – progression from normouricemia to asymptomatic hyperuricemia and subsequently to gout – with previous genome-wide analyses mainly focusing on genes associated with the first step.

Hirotaka Matsuo (National Defense Medical College, Tokorozawa) and co-researchers, however, focused on the second step, conducting a GWAS in 945 men with clinically defined gout and 1003 men with asymptomatic hyperuricemia, and replicating the analysis in two additional case–control cohorts.

A meta-analysis of all three cohorts – including a total of 2860 and 3149 men with gout and asymptomatic hyperuricemia, respectively – identified two loci associated with gout susceptibility at genome-level significance, namely rs7927466, an intronic single nucleotide polymorphism (SNP) of CNTN5, and rs9952962, an intergenic SNP located near MIR302F.

A third SNP – rs12980365, also an intergenic SNP, this time located near ZNF724 – was also likely linked to progression from asymptomatic hyperuricemia to gout, but this association was less robust.

The investigators also compared the odds ratios for the three genetic loci identified in this study with those for 10 loci detected in a previous GWAS comparing gout patients and normouricemic individuals. The analysis revealed a distinct pattern “clearly indicating that these novel loci are associated with distinct mechanisms of gout development,” they write in the Annals of the Rheumatic Diseases.

Discussing the three novel gout loci, the team notes that CNTN5 has previously been associated with other inflammatory diseases, such as ankylosing spondylitis and Behçet’s disease, while a different CNTN5 SNP has been linked to tumor necrosis factor inhibitor response in individuals with rheumatoid arthritis.

Matsuo et al add that although various microRNAs have been shown to be involved in the pathogenesis of other forms of inflammatory arthritis, the specific role of MIR302F remains unknown, as does the function of ZNF724.

They point out, however, the possibility that the loci detected in the current GWAS “are just surrogate markers and that other genes including ZNF730 and IPO5P1 near these SNPs are the true risk loci for gout development.”

By Shreeya Nanda

medwireNews is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group

Ann Rheum Dis 2019; doi:10.1136/annrheumdis-2019-215521

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