DOCTOR'S VIEW ARCHIVEMedical Authors and Editors Barbara K. Hecht, Ph.D. and Frederick Hecht, M.D.
There are basically two types of gene mutations in respect to disease. One type of mutation causes a disease. For example, the mutant gene may cause achrondroplasia (a form of dwarfism) or it may cause hemophilia or cystic fibrosis or sickle cell disease. The existence of genes that cause diseases has long been recognized.
The other type of gene mutation does not directly cause a disease but rather predisposes to it. These genes make a person susceptible to developing a disease. These susceptibility genes often involve common chronic diseases such as diabetes and rheumatoid arthritis.
An important finding has just been made about the genetic susceptibility to rheumatoid arthritis and autoimmunity. We will outline the finding.
Background: Rheumatoid arthritis is the most common systemic autoimmune disease. It affects 1% of all adults in the world. The disease is characterized by immune-mediated destruction of the joint architecture. It is 2 to 3 times more common in women than men. The heritability of rheumatoid arthritis is 60%, reflecting a strong genetic component in the disease.
Design of Research: To identify genes involved in the susceptibility to rheumatoid arthritis, a "discovery study" was done testing for 87 variations called SNPs (single-nucleotide polymorphisms) in candidate genes and regions. The discovery study involved 475 individuals with rheumatoid arthritis and 475 individually matched controls.
Result: One of the SNPs was found to be associated with rheumatoid arthritis. It was a "missense" SNP in a gene encoding a protein tyrosine phosphorylase. This risk SNP was present in 28% of those with rheumatoid arthritis and 17% of the controls
Comment: A variant of this same SNP encoding the same phosphorylase enzyme was recently found associated with type 1 diabetes, another autoimmune disease. It is beginning to look as if this variant phosphatase may increase the overall reactivity of the immune system and may raise the risk for autoimmune disease.
Source: Ann B. Begovich and co-authors. A Missense Single-Nucleotide Polymorphism in a Gene Encoding a Protein Tyrosine Phosphatase (PTPN22) Is Associated with Rheumatoid Arthritis. Am. J. Hum. Genet., 75:000, 2004 (published online on June 18, 2004 by the American Journal of Human Genetics)