A Candidate Gene Approach Identifies the TRAF1/C5 Region as a Risk Factor for Rheumatoid Arthritis
2007

Identifying a Genetic Risk Factor for Rheumatoid Arthritis

Sample size: 2718 publication Evidence: high

Author Information

Author(s): Kurreeman Fina A. S, Padyukov Leonid, Marques Rute B, Schrodi Steven J, Seddighzadeh Maria, Stoeken-Rijsbergen Gerrie, van der Helm-van Mil Annette H. M, Allaart Cornelia F, Verduyn Willem, Houwing-Duistermaat Jeanine, Alfredsson Lars, Begovich Ann B, Klareskog Lars, Huizinga Tom W. J, Toes Rene E. M

Primary Institution: Leiden University Medical Centre

Hypothesis

The immune-related genes complement component 5 (C5) and/or TNF receptor-associated factor 1 (TRAF1) are relevant candidate genes for rheumatoid arthritis (RA).

Conclusion

A polymorphism in the TRAF1/C5 region increases susceptibility to and severity of rheumatoid arthritis.

Supporting Evidence

  • Significant association of SNPs located in a haplotype block that encompasses the 3′ end of C5 and TRAF1.
  • Replication of findings in three independent sample sets from the Netherlands, Sweden, and the US.
  • Association with increased disease progression as determined by radiographic damage over time.

Takeaway

Scientists found a gene that makes some people more likely to get rheumatoid arthritis, a disease that causes painful swelling in the joints.

Methodology

A case-control study using 40 SNPs from the TRAF1/C5 region in RA patients and controls, followed by replication in three independent sample sets.

Limitations

The causative variation is not yet known, and the study may be underpowered to exclude associations with autoantibody-negative disease.

Participant Demographics

Participants included 290 RA patients and 254 controls of Dutch origin, with additional samples from Sweden and the US.

Statistical Information

P-Value

1.40 × 10−8

Confidence Interval

95% CI 1.17–1.39

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pmed.0040278

Want to read the original?

Access the complete publication on the publisher's website

View Original Publication