Association between functional FCGR3A F158V and FCGR2A R131H polymorphisms and responsiveness to rituximab in patients with autoimmune diseases: a meta-analysis

Pharmacogenomics J. 2023 Nov;23(6):210-216. doi: 10.1038/s41397-023-00308-9. Epub 2023 May 6.

Abstract

Objectives: To investigate the association between the functional Fc gamma receptor 3 A (FCGR3A) V158F and FCGR2A R131H polymorphisms and rituximab therapy in patients with autoimmune diseases.

Methods: We searched the Medline, Embase, and Cochrane databases for relevant articles. We conducted a meta-analysis of the association between FCGR3A V158F and FCGR2A R131H polymorphisms and responsiveness to rituximab in patients with autoimmune diseases.

Results: Eleven studies, consisting of 661 responders and 267 non-responders for FCGR3A V158F polymorphism and 156 responders and 89 non-responders for FCGR2A R131H polymorphism, were included. The meta-analysis revealed a significant association between the FCGR3A V allele and responsiveness to rituximab (odds ratio [OR] = 1.600, 95% confidence interval [CI] = 1.268-2.018, P < 0.001). Furthermore, associations were found using the dominant and homozygous contrast models. Subgroup analysis showed an association between the FCGR3A V allele and responsiveness to rituximab in European, RA, ITP, small (<50) and large (≥50) groups, and short- (≤6 months) and long-term follow-up periods (≥6 months). These associations were also found in recessive, dominant or homozygous contrast models. Meta-analysis revealed no association between the FCGR2A R allele and responsiveness to rituximab (OR = 1.243, 95% CI = 0.825-1.873, P = 0.229).

Conclusions: We demonstrated that the FCGR3A F158V polymorphism is associated with better responsiveness to rituximab therapy in patients with autoimmune diseases, indicating that individuals carrying the FCGR3A V allele will likely respond better to rituximab. However, FCGR2A R131H polymorphism was not associated with better response to rituximab.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Arthritis, Rheumatoid*
  • Autoimmune Diseases* / drug therapy
  • Autoimmune Diseases* / genetics
  • Genotype
  • Humans
  • Polymorphism, Genetic
  • Polymorphism, Single Nucleotide / genetics
  • Receptors, IgG / genetics
  • Rituximab / therapeutic use

Substances

  • Rituximab
  • Receptors, IgG
  • FCGR2A protein, human
  • FCGR3A protein, human