The runt-related transcription factor 1 (RUNX1, also called AML1; gene map locus 21q22.3) has recently been identified as an important gene in determining susceptibility to several autoimmune diseases (Alarcon-Riquelme, 2003; Coutinho, 2004).

RUNX1 interacts with the programmed cell death 1 gene (PDCD1, also called PD-1; gene map locus 2q37.3) to determine susceptibility to systemic lupus erythematosus (SLE) (Prokunina et al, 2002) and type 1 diabetes (Nielsen et al., 2003).

In addition, RUNX1 binds to a site between SLC9A3R1 (Solute Carrier Family 9, Isoform A3, Regulatory Factor 1) and NAT9 (a member of the N-acetyltransferase family) to determine susceptibility to psoriasis (Helms et al., 2003). SLC9A3R1 is located on chromosome 17, in the same region as the psoriasis susceptibility 2 (PSORS2) gene (gene map locus 17q25).

RUNX1 also interacts with SLC22A4 (gene map locus 5q31) encoding an organic cation transporter (where SLC stands for "solute carrier"), to determine susceptibility to rheumatoid arthritis (Tokuhiro et al., 2003). SLC22A4 is now known to be the IBD5 gene (gene map locus 5q31) which interacts with the IBD1 (NOD2/CARD15) gene (gene map locus 16q12), the major gene determining susceptibility to Crohn's disease (Peltekova et al., 2004).

This begs the question, is there a link between RUNX1 and ulcerative colitis and/or PSC? It seems that there is. RUNX1 has recently been shown to regulate the expression of the tissue inhibitor of metalloproteinase-1 (TIMP1) gene (gene map locus Xp11.3-p11.23) (Bertrand-Philippe et al., 2004). It is known that there is an imbalance in expression of metalloproteinases (MMPs) (such as stromelysin-1 = MMP3) and their inhibitors (such as TIMP1) in inflammatory bowel disease (Heuschkel et al., 2000), including Crohn's (Schuppan and Freitag, 2004) and ulcerative colitis (Wiercinska-Drapalo et al., 2003). Moreover, a polymorphism in the metalloproteinase gene (MMP3) encoding stromelysin-1 (gene map locus 11q23) may influence susceptibility and disease progression in PSC (Satsangi et al., 2001). The MMP3 gene in turn affects disease progression in rheumatoid arthritis (Constantin et al., 2002).

Further studies of the RUNX1 transcription factor and its interacting partners may clarify the genetic basis of other autoimmune diseases.

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