DOCTOR'S VIEW ARCHIVE

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 Autoimmunity

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.

Perspective

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.

Original Sources:

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, 2002 doi:10.1038/ng1020.
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

Psoriasis (main article)
Psoriasis Center

Lupus

Lupus Fact Sheet
Lupus
Lupus Center
Focus Topics on Arthritic Conditions, edited by William C. Shiel, Jr., MD, FACP, FACR, Rheumatology Specialist and Chief Medical Editor, MedicineNet.com

Rheumatoid Arthritis

Rheumatoid Arthritis
Rheumatoid Factor
Rheumatoid Arthritis: A Day In The Life Of A Patient
Rheumatoid Arthritis - When Do I Call The Doctor?
Rheumatoid Arthritis Center

QUESTION

The term arthritis refers to stiffness in the joints. See Answer

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