DOCTOR'S VIEW ARCHIVE
Psoriasis, Lupus,Rheumatoid ArthritisShare
Medical 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
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
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,
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,
For additional information, please see the following MedicineNet.com areas:
Last Editorial Review: 12/29/2004