title: Copy number variation of the gene NCF1 is associated with rheumatoid arthritis.
abstract: OBJECTIVE
  The aim of this study was to investigate genetic variants in the gene neutrophil cytosolic factor 1 (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 five 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 nonfunctional pseudogenes, nearly identical in sequence to NCF1. We have characterized 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 with 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 reactive oxygen species production.
  
  
  METHODS
  This is the first finding of genetic association of NCF1 with RA. The detailed characterization of genetic variants in NCF1 also helps elucidate the complexity of the NCF1 gene.
  
  
  CONCLUSIONS
  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 phagocyte NADPH oxidase complex in RA pathogenesis.
authors: Medical Inflammation Research, Department of Experimental Medical Science, Lund University, Sweden.
authors: Lina M
authors: LM
authors: Olsson
authors: Annika
authors: A
authors: Nerstedt
authors: Anna-Karin
authors: AK
authors: Lindqvist
authors: Sa C M
authors: SC
authors: Johansson
authors: Patrik
authors: P
authors: Medstrand
authors: Peter
authors: P
authors: Olofsson
authors: Rikard
authors: R
authors: Holmdahl
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D016022:Case-Control Studies; D056915:DNA Copy Number Variations; D005260:Female; D018628:Gene Dosage; D023061:Gene Order; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D019255:NADPH Oxidases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017382:Reactive Oxygen Species / Q000378:metabolism; D055815:Young Adult
chemical_list: D017382:Reactive Oxygen Species; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1