Association of PADI4 Gene Polymorphisms With Susceptibility to Rheumatoid Arthritis: Evidence From 24 Case-Control Studies

Int J Immunogenet. 2025 Feb;52(1):1-23. doi: 10.1111/iji.12701. Epub 2024 Nov 9.

Abstract

This study aims to investigate the association of rs11203366, rs11203367, rs874881, rs2240340 and rs1748033 polymorphisms of protein-arginine deiminase type 4 (PADI4) gene with the risk of rheumatoid arthritis (RA) through a meta-analysis that was followed with a bioinformatics approach. The data were collected from reputable articles and underwent quantitative analysis, followed by in silico analysis using some bioinformatics tools. The results showed that rs874881 polymorphism in Latino (G vs. C: OR = 1.35, 95% CI = 1.11-1.65, p = 0.003; GG + CG vs. CC: OR = 2.02, 95% CI = 1.41-2.89, p = 0.0001; CG vs. CC + GG: OR = 1.38, 95% CI = 1.04-1.83, p = 0.027; GG vs. CC: OR = 2.09, 95% CI = 1.35-3.23, p = 0.001; CG vs. CC: OR = 1.98, 95% CI = 1.36-2.87, p = 0.00033) and rs1748033 in Caucasian population (T vs. C: OR = 1.25, 95% CI = 1.07-1.45, p = 0.005; TT vs. CT + CC: OR = 1.34, 95% CI = 1.09-1.64, p = 0.005, TT + CT vs. CC: OR = 1.26, 95% CI = 1.09-1.44, p = 0.001; TT vs. CC: OR = 1.59, 95% CI = 1.13-2.23, p = 0.007; CT vs. CC: OR = 1.20, 95% CI: 1.04-1.39, p = 0.015) are associated with increased risk of RA. Moreover, rs11203366 (G vs. A: OR = 1.46, 95% CI = 1.19-1.78, p = 0.0002, GG vs. AG + AA: OR = 1.42, 95% CI = 1.01-2.01, p = 0.043; GG + AG vs. AA: OR = 2.03, 95% CI = 1.45-2.86, p = 0.00004; GG vs. AA: OR = 2.29, 95% CI = 1.49-3.51, p = 0.0002; AG vs. AA: OR = 1.93, 95% CI = 1.35-2.76, p = 0.0003) and rs11203367 (T vs. C: OR = 1.50, 95% CI = 1.23-1.83, p = 0.00007; TT vs. CT + CC: OR = 1.56, 95% CI = 1.12-2.18, p = 0.009; TT + CT vs. CC: OR = 2.02, 95% CI = 1.43-2.84, p = 0.00007, TT vs. CC: OR = 2.43, 95% CI = 1.59-3.71, p = 0.0004; CT vs. CC: OR = 1.86, 95% CI = 1.30-2.68, p = 0.0007) had an impact in the Latino population. Bioinformatics tools showed the effect of these polymorphisms on gene function. These findings suggest that rs11203366, rs11203367, rs874881 and rs1748033 polymorphisms may be genetic risk factors for RA. Moreover, differences between populations suggest that ethnicity may play an important role in the effect of these polymorphisms on RA risk.

Keywords: PADI4; bioinformatics; genetic polymorphism; meta‐analysis; rheumatoid arthritis.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Alleles
  • Arthritis, Rheumatoid* / genetics
  • Case-Control Studies
  • Genetic Association Studies*
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Polymorphism, Single Nucleotide*
  • Protein-Arginine Deiminase Type 4* / genetics
  • Protein-Arginine Deiminases / genetics
  • Risk Factors
  • White People / genetics

Substances

  • Protein-Arginine Deiminase Type 4
  • PADI4 protein, human
  • Protein-Arginine Deiminases