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Three New Genes Implicated in Rheumatoid Arthritis

Researchers use microarray analysis of monozygotic twins discordant for rheumatoid arthritis

THURSDAY, June 29 (HealthDay News) -- Using complementary DNA microarray analysis of blood samples from disease-discordant monozygotic twins, researchers have identified three new genes that appear to play a role in rheumatoid arthritis, according to a report in the July issue of Arthritis & Rheumatism.

Among the 11 pairs of twins, 1,163 transcripts were significantly differentially expressed in their lymphoblastoid B cell lines. Of these, 747 were overexpressed and 416 were underexpressed, report researchers led by Joseph Holoshitz, M.D., of the University of Michigan Medical Center in Ann Arbor, Mich.

The most significantly overexpressed gene was laeverin, a novel enzyme that degrades proteins, followed by 11β-hydroxysteroid dehydrogenase type 2 (11β HSD2), a steroid pathway enzyme linked to inflammation and bone erosion. The third was cysteine-rich, angiogenic inducer 61 (Cyr61), which is known to play a role in angiogensis. The products of these newly identified genes were all overexpressed in rheumatoid arthritis synovial tissues and 11β HSD2 was also overexpressed in synovial tissue of osteoarthritis patients.

"Although the pathogenic role of the newly reported genes remains to be determined, the representation of many established pannus-associated genes in this analysis suggests that this approach could provide mechanistic insights into the pathogenesis of rheumatoid arthritis and could help identify novel candidate targets for therapeutic interventions," study authors conclude.

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