Six Genetic Loci Linked to Rheumatoid Arthritis Risk

Study supports role of CD40 signaling pathway -- already eyed in drug development -- in disease

WEDNESDAY, Sept. 17 (HealthDay News) -- The CD40 signaling pathway appears to be important in rheumatoid arthritis, and five other gene loci may be associated with the disease, according to research published online Sept. 14 in Nature Genetics.

Soumya Raychaudhuri, Ph.D., of the Broad Institute of Harvard and Massachusetts Institute of Technology in Cambridge, Mass., and colleagues performed a meta-analysis of single nucleotide polymorphism (SNP) data from European subjects in two genomewide association studies. They then genotyped 31 SNPs in an independent replication of cases and matched controls from eight collections.

The researchers identified associations between the disease and the CD40 and CCL21 gene loci, and found evidence of association in four other loci: CDK6 (which appears to play a role in the rapid proliferation of B cells and CD8 memory cells), PRKCQ (which encodes a kinase needed for the activation of NF-κB and AP-1), MMEL1-TNFRSF14, and KIF5A-PIP4K2C.

"These associations provide strong evidence for the importance of the CD40 signaling pathway in autoantibody-positive rheumatoid arthritis. Our study implicates a putative functional variant that affects protein translation of the CD40 receptor. Established associations near TRAF1 and TNFAIP3 (also known as A20) already suggest the possibility that the CD40 signaling pathway mediates rheumatoid pathogenesis through NF-κB activation, although the rheumatoid arthritis risk variants have not yet been proven to modulate function of these genes," the authors write.

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