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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 (P meta  = 3.16 × 10 -4 , OR with 95% CI: 1.39 [1.17-1.66] for rs10821905 of A1CF, P meta  = 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.

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