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<p>Gout is a widespread autoinflammatory arthritis primarily driven by hyperuricemia, with genetic and environmental factors influencing disease susceptibility. Genetic variants in the ABCG2 and NLRP3 genes have been implicated in urate transport and inflammatory responses, respectively. This meta-analysis aimed to assess the association of NLRP3 (rs10754558, rs3806268, rs12137901) and ABCG2 (rs2231142) polymorphisms with gout risk in Asian and Caucasian populations. A systematic search following PRISMA guidelines was conducted across Web of Science, Scopus, PubMed, and Embase databases. Eleven case–control studies were included, covering 6236 gout cases and 16,007 controls for NLRP3 variants, and 2875 cases and 12,495 controls for ABCG2. Data were analysed using odds ratios (ORs) and 95% confidence intervals (CIs). Heterogeneity was assessed through I<sup>2</sup> statistics, and publication bias was evaluated using Egger’s test. The results showed no significant association between the NLRP3 polymorphisms and gout risk across all genetic models. In contrast, ABCG2 rs2231142 demonstrated a strong and consistent association with gout susceptibility in allelic (OR 0.4, 95% CI 0.2–0.6, <i>p</i> = 3.7703e−06), recessive (OR 0.4, 95% CI 0.2–0.6, <i>p</i> = 0.0001), and dominant models (OR 0.2, 95% CI 0.1–0.4, <i>p</i> = 6.99e−08). These findings suggest that although NLRP3 variants may not predict susceptibility to gout, the inflammasome pathway remains critical in disease pathogenesis. While the ABCG2 (rs2231142) exhibits that the A allele confers increased gout risk, and the C allele is protective. Further investigations into phenotype-specific associations and molecular mechanisms are warranted to elucidate the genetic underpinnings of gout comprehensively.</p>

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Association of NLRP3 (rs10754558, rs3806268, rs12137901) and ABCG2 (rs2231142) Gene Polymorphisms in Gout Susceptibility Among Asian and Caucasian Populations: A Meta-Analysis

  • 期刊论文

  • 发表日期：

    2026年1月28日

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  • Sharon Benita Stephen,
  • Niranjan Gopal,
  • R. Muthuvel,
  • S. Waheeda,
  • Gowtham Kumar Subbaraj

摘要

Gout is a widespread autoinflammatory arthritis primarily driven by hyperuricemia, with genetic and environmental factors influencing disease susceptibility. Genetic variants in the ABCG2 and NLRP3 genes have been implicated in urate transport and inflammatory responses, respectively. This meta-analysis aimed to assess the association of NLRP3 (rs10754558, rs3806268, rs12137901) and ABCG2 (rs2231142) polymorphisms with gout risk in Asian and Caucasian populations. A systematic search following PRISMA guidelines was conducted across Web of Science, Scopus, PubMed, and Embase databases. Eleven case–control studies were included, covering 6236 gout cases and 16,007 controls for NLRP3 variants, and 2875 cases and 12,495 controls for ABCG2. Data were analysed using odds ratios (ORs) and 95% confidence intervals (CIs). Heterogeneity was assessed through I2 statistics, and publication bias was evaluated using Egger’s test. The results showed no significant association between the NLRP3 polymorphisms and gout risk across all genetic models. In contrast, ABCG2 rs2231142 demonstrated a strong and consistent association with gout susceptibility in allelic (OR 0.4, 95% CI 0.2–0.6, p = 3.7703e−06), recessive (OR 0.4, 95% CI 0.2–0.6, p = 0.0001), and dominant models (OR 0.2, 95% CI 0.1–0.4, p = 6.99e−08). These findings suggest that although NLRP3 variants may not predict susceptibility to gout, the inflammasome pathway remains critical in disease pathogenesis. While the ABCG2 (rs2231142) exhibits that the A allele confers increased gout risk, and the C allele is protective. Further investigations into phenotype-specific associations and molecular mechanisms are warranted to elucidate the genetic underpinnings of gout comprehensively.