Copy number variation of the gene NCF1 is associated with Rheumatoid Arthritis.

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Aims The aim of this study was to investigate genetic variants in the gene NCF1 for association with Rheumatoid Arthritis (RA). In rodent models, a single nucleotide polymorphism (SNP) in Ncf1 has been shown to be a major locus regulating severity of arthritis. Ncf1 encodes one of 5 subunits of the NADPH oxidase complex. In humans the genomic structure of NCF1 is complex, excluding it from genome wide association screens and complicating genetic analysis. In addition to copy number variation of NCF1, there are also two non-functional pseudogenes, nearly identical in sequence to NCF1. We have characterised copy number variation and SNPs in NCF1, and investigated these variants for association with RA. Results We find that RA patients are less likely to have an increased copy number of NCF1, 7.6%, compared to 11.6% in controls; P = 0.037. We also show that the T-allele of NCF1-339 (rs13447) is expressed in NCF1 and significantly reduces ROS production. Innovation This is the first finding of genetic association of NCF1 with RA. The detailed characterisation of genetic variants in NCF1 also help elucidate the complexity of the NCF1 gene. Conclusion These data suggest that an increased copy number of NCF1 can be protective against developing RA and add support to previous findings of a role of NCF1 and the NOX2 complex in RA pathogenesis.


  • Lina Olsson
  • Annika Nerstedt
  • Anna-Karin Lindqvist
  • Åsa Johansson
  • Patrik Medstrand
  • Peter Olofsson
  • Rikard Holmdahl
Enheter & grupper

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Cell- och molekylärbiologi
Sidor (från-till)71-78
TidskriftAntioxidants & Redox Signaling
Utgåva nummer1
StatusPublished - 2012
Peer review utfördJa