RESEARCH - Identification of genes modulated in RA using complementary DNA microarray analysis in twins

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Arthritis Rheum. 2006 Jun 27;54(7):2047-2060 [Epub ahead of print]

Identification of genes modulated in rheumatoid arthritis using

complementary DNA microarray analysis of lymphoblastoid B cell lines from

disease-discordant monozygotic twins.

Haas CS, Creighton CJ, Pi X, Maine I, Koch AE, Haines GK 3rd, Ling S,

Chinnaiyan AM, Holoshitz J.

University of Michigan Medical Center, Ann Arbor.

OBJECTIVE: To identify disease-specific gene expression profiles in patients

with rheumatoid arthritis (RA), using complementary DNA (cDNA) microarray

analyses on lymphoblastoid B cell lines (LCLs) derived from RA-discordant

monozygotic (MZ) twins. METHODS: The cDNA was prepared from LCLs derived

from the peripheral blood of 11 pairs of RA-discordant MZ twins. The RA twin

cDNA was labeled with cy5 fluorescent dye, and the cDNA of the healthy

co-twin was labeled with cy3. To determine relative expression profiles,

cDNA from each twin pair was combined and hybridized on 20,000-element

microarray chips. Immunohistochemistry and real-time polymerase chain

reaction were used to detect the expression of selected gene products in

synovial tissue from patients with RA compared with patients with

osteoarthritis and normal healthy controls. RESULTS: In RA twin LCLs

compared with healthy co-twin LCLs, 1,163 transcripts were significantly

differentially expressed. Of these, 747 were overexpressed and 416 were

underexpressed. Gene ontology analysis revealed many genes known to play a

role in apoptosis, angiogenesis, proteolysis, and signaling. The 3 most

significantly overexpressed genes were laeverin (a novel enzyme with

sequence homology to CD13), 11beta-hydroxysteroid dehydrogenase type 2 (a

steroid pathway enzyme), and cysteine-rich, angiogenic inducer 61 (a known

angiogenic factor). The products of these genes, heretofore uncharacterized

in RA, were all abundantly expressed in RA synovial tissues.

CONCLUSION: Microarray cDNA analysis of peripheral blood-derived LCLs from

well-controlled patient populations is a useful tool to detect RA-relevant

genes and could help in identifying novel therapeutic targets.

PMID: 16804865

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

6804865

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