Genetics of RA unfolding

[Guest guest]

Malorye Branca

Senior Informatics Editor

BioIT World

Jun 25, 2003

Major Groove:

Genetics of Rheumatoid Arthritis Unfolding

With so much attention on cancer, one often forgets that

pharmacogenomics is being applied to a huge range of diseases and

therapies. For example, European scientists have just published

pharmacogenomic findings that provide new insights about the genetic

underpinnings of rheumatoid arthritis (RA).

In one study, scientists from Institute Cochin in Paris found 63 genes

that appear to be linked with development of the disease. The group, led

by Gilles Chiocchia, used their own spotted arrays to study and compare

the expression of 5200 genes in the synovial fluid of a group of

patients with RA and another group with osteoarthritis.

They found 48 known and 15 unknown genes that were either overexpressed

or underexpressed in RA patients compared to those with osteoarthritis.

Two of the novel genes were located on chromosome 6, at the p21

region-an area already linked to inflammatory disease. Four other genes

are located on the X chromosome.

According to a press release from Reuters Health, the French scientists

hope their findings will lead to the identification of new pathways

related to RA, and that new diagnostics and treatments can spring from

this. The group announced their findings at the recent Annual European

Congress of Rheumatology.

In a related study, researchers at hospital Xeral-Calde in Lugo, Spain,

used a genotyping approach to see if the risk of cardiovascular disease

in chronic RA patients has a genetic component. That study was led by

A. -Gay, and is published in the American Journal of

Medicine, 2003;114:647-652.

-Gay and colleagues genotyped the HLA-DR1 allele in 31 people

without RA and 55 patients who had had at least five years of RA

treatment. The patients also had to be currently taking at least one

disease-modifying RA drug.

Besides gathering genotype data, the researchers looked at study

participants' vasodilation response using brachial artery

ultrasonography, both after release of an inflated blood pressure cuff

at the wrists and after a dose of nitroglycerin. The first test measures

" endothelium-dependent " vasodilation, while the second measures the

" endothelium-independent " response.

Overall, the RA patients' endothelium-dependent vasodilation response

was significantly lower than that of the controls. Among the RA

patients, those with the HLA-DRB1*04 or HLA-DRB1*0404 alleles had a

significantly lower response than the rest, leading the investigators to

speculate that these alleles could increase the risk of cardiovascular

disease.

The genetics of diseases like RA are going to be much more complicated

to study and understand, because they are thought to involve multiple

diseases and risk factors. These studies are intriguing first steps into

this incredibly challenging new field, where many of the " rules " are

still being learned.

http://www.bio-itworld.com/archive/files/062503.html

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org