DOCTOR'S VIEW ARCHIVEMedical Author: Frederick Hecht, M.D.
Medical Editor: Barbara Hecht, Ph.D.
Nov. 11, 2000 -- Changes in one gene have been discovered that are shared by three common autoimmune diseases -- the skin condition psoriasis as well as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). The genetic changes involve a gene called Runx-1.
What is Runx-1?
Runx-1 is a protein that acts as a transcription factor. It controls when genes are switched on or off. Runx-1 does so by binding to regulatory sequences -- specific sequences of DNA -- that are close to the genes they regulate. These DNA sequences, called Runx-1 binding sites, are scattered throughout the human genome, wherever there is a gene under the control of Runx-1.
Runx-1 stands for runt-related transcription factor 1. Runx-1 is also called AML1 because it is also altered in a form of acute myeloid leukemia, but that is a very different story, one to be told another time.
The Tie-in with
Changes in Runx-1 appear to contribute to autoimmune diseases. A Runx-1 binding site on chromosome 2 is altered in many patients with systemic lupus erythematosus. Many psoriasis patients have a changed Runx-1 binding site on chromosome 17. And a Runx-1 binding site on chromosome 17 is changed in patients with rheumatoid arthritis. Thus, there are genetic connections, some involving Runx-1, between diverse autoimmune diseases.
The Tie-in with Lupus
The tie-in between Runx-1 and lupus is not new. It was reported back in 2002 by Ludmila Prokunina and her colleagues from Sweden. They found that a polymorphism (a normal variation) in the programmed cell death 1 gene dubbed PDCD1 was associated with susceptibility to systemic lupus erythematosus. They traced this down and found that it reflected an altered binding site for Runx-1.
The Tie-ins with Psoriasis and Rheumatoid Arthritis
The reports linking Runx-1 to psoriasis and to rheumatoid arthritis are very new. They were just published back-to-back online in the journal Nature Genetics on November 9. The work on psoriasis was from a multicenter American research effort while that on rheumatoid arthritis emanated from Japan.
The fact that Runx-1 is involved in at least three common autoimmune diseases is clearly remarkable and noteworthy. It is also clear that the changes in Runx-1 do not cause these diseases. Runx-1 is a susceptibility gene locus, or loci, since there are Runx-1 binding sites strewn about the genome. Changes in these different Runx-1 sites make a person vulnerable to these different autoimmune diseases.
Runx-1 appears to be one piece in the autoimmune disease puzzle.
1. Prokunina, L. et al., A
regulatory polymorphism in PDCD1 is associated with susceptibility to systemic
lupus erythematosus in humans. Nature Genetics, Published online: October 28,
2. Helms, C. et al., A putative RUNX1 binding site variant between SLC9A3R1 and NAT9 is associated with susceptibility to psoriasis. Nature Genetics. Published online: 9 November 2003, doi:10.1038/ng1268.
3. Tokuhiro, S. et al., An intronic SNP in a RUNX1 binding site of SLC22A4, encoding an organic cation transporter, is associated with rheumatoid arthritis. Nature Genetics. Published online: 9 November 2003, doi:10.1038/ng1267.
For additional information, please see the following MedicineNet.com areas:
- Psoriasis (main article)
- Psoriasis Center