Both variants of A1CF and BAZ1B genes are associated with gout susceptibility: a replication study and meta-analysis in a Japanese population

Abstract

Gout is a common type of acute arthritis that results from elevated serum uric acid (SUA) levels. Recent genome-wide association studies (GWASs) have revealed several novel single nucleotide polymorphism (SNPs) associated with SUA levels. Of these, rs10821905 of A1CF and rs1178977 of BAZ1B showed the greatest and the second greatest significant effect size for increasing SUA level in the Japanese population, but their association with gout is not clear. We examined their association with gout using 1411 clinically-defined Japanese gout patients and 1285 controls, and meta-analyzed our previous gout GWAS data to investigate any association with gout. Replication studies revealed both SNPs to be significantly associated with gout (P = 0.0366, odds ratio [OR] with 95% confidence interval [CI]: 1.30 [1.02–1.68] for rs10821905 of A1CF, P = 6.49 × 10–3, OR with 95% CI: 1.29 [1.07–1.55] for rs1178977 of BAZ1B). Meta-analysis also revealed a significant association with gout in both SNPs (Pmeta = 3.16 × 10–4, OR with 95% CI: 1.39 [1.17–1.66] for rs10821905 of A1CF, Pmeta = 7.28 × 10–5, OR with 95% CI 1.32 [1.15–1.51] for rs1178977 of BAZ1B). This study shows the first known association between SNPs of A1CF, BAZ1B and clinically-defined gout cases in Japanese. Our results also suggest a shared physiological/pathophysiological background between several populations, including Japanese, for both SUA increase and gout susceptibility. Our findings will not only assist the elucidation of the pathophysiology of gout and hyperuricemia, but also suggest new molecular targets.

Trends in the Contribution of Genetic Susceptibility Loci to Hyperuricemia and Gout and Associated Novel Mechanisms

“…Makoto et al further investigated the association between the A1CF SNP (rs10821905) and gout in Japanese individuals. They found that it was significantly associated with elevated serum uric acid and gout via a mechanism that might involve the regulation of dyslipidemia and uric acid metabolism ( Kawaguchi et al, 2021 ). Further investigation of the mechanism of interaction between alcohol and AICF could suggest that the metabolite acetate of alcohol (ethanol) leads to the increased production of diacylglycerol and further activates protein kinase C and AICF phosphorylation in the nucleus.…”

Exploring metabolic changes in gout – Insights from a genetic study

“…Previous genome-wide association studies (GWASs) 1 have identified numerous loci associated, with gout, a common inflammatory joint disease caused by the crystallization of urate inside the joints 2 . These findings have provided valuable information about key goutrelated risk factors, such as hyperuricemia and joint diseases [3][4][5][6][7][8][9][10] . However, the genetic factors underlying gout remain incompletely understood.…”

Susceptibility genes of hyperuricemia and gout

“…In other words, when ABCG2 dysfunctional variation and A1CF variation exist at the same time, A1CF variation is significantly correlated with gout, but in the absence of ABCG2 variation, the correlation between A1CF variation and gout is no longer significant. However, the BAZ1B variation has a significant correlation with gout with or without ABCG2 dysfunctional variation [ 74 ]. It can be seen that ABCG2 gene variants and their SNPs are not only risk factors for HUA and gout, but also increase the risk of HUA and gout via interacting with other gene variants.…”