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  • Title: Positional identification of Ncf1 as a gene that regulates arthritis severity in rats.
    Author: Olofsson P, Holmberg J, Tordsson J, Lu S, Akerström B, Holmdahl R.
    Journal: Nat Genet; 2003 Jan; 33(1):25-32. PubMed ID: 12461526.
    Abstract:
    The identification of genes underlying quantitative-trait loci (QTL) for complex diseases, such as rheumatoid arthritis, is a challenging and difficult task for the human genome project. Through positional cloning of the Pia4 QTL in rats, we found that a naturally occurring polymorphism of Ncf1 (encoding neutrophil cytosolic factor 1, a component of the NADPH oxidase complex) regulates arthritis severity. The disease-related allele of Ncf1 has reduced oxidative burst response and promotes activation of arthritogenic T cells. Pharmacological treatment with substances that activate the NADPH oxidase complex is shown to ameliorate arthritis. Hence, Ncf1 is associated with a new autoimmune mechanism leading to severe destructive arthritis, notably similar to rheumatoid arthritis in humans.
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