RESEARCH - Replication of TRAF1 and C5 as a susceptibility locus for RA

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Arthritis Rheum. 2008 Sep;58(9):2670-4.

Replication of the tumor necrosis factor receptor-associated factor

1/complement component 5 region as a susceptibility locus for

rheumatoid arthritis in a European family-based study.

Kurreeman FA, Rocha D, Houwing-Duistermaat J, Vrijmoet S, Teixeira VH,

Migliorini P, Balsa A, Westhovens R, Barrera P, Alves H, Vaz C,

Fernandes M, Pascual-Salcedo D, Michou L, Bombardieri S, Radstake T,

van Riel P, van de Putte L, Lopes-Vaz A, Prum B, Bardin T, Gut I,

Cornelis F, Huizinga TW, Petit-Teixeira E, Toes RE; European

Consortium on Rheumatoid Arthritis Families.

Leiden University Medical Center, Leiden, The Netherlands.

OBJECTIVE: We recently showed, using a candidate gene approach in a

case-control association study, that a 65-kb block encompassing tumor

necrosis factor receptor-associated factor 1 (TRAF1) and C5 is

strongly associated with rheumatoid arthritis (RA). Compared with

case-control association studies, family-based studies have the added

advantage of controlling potential differences in population structure

and are not likely to be hampered by variation in population allele

frequencies, as is seen for many genetic polymorphisms, including the

TRAF1/C5 locus. The aim of this study was to confirm this association

in populations of European origin by using a family-based approach.

METHODS: A total of 1,356 western European white individuals from 452

" trio " families were genotyped for the rs10818488 polymorphism, using

the TaqMan allelic discrimination assay.

RESULTS: We observed evidence for association, demonstrating departure

from Mendel's law, with an overtransmission of the rs10818488 A allele

(A = 55%; P = 0.036). By taking into consideration parental

phenotypes, we also observed an increased A allele frequency in

affected versus unaffected parents (A = 64%; combined P = 0.015).

Individuals carrying the A allele had a 1.2-fold increased risk of

developing RA (allelic odds ratio 1.24, 95% confidence interval

1.04-1.50).

CONCLUSION: Using a family-based study that is robust against

population stratification, we provide evidence for the association of

the TRAF1/C5 rs10818488 A allele and RA in populations of European

descent, further substantiating our previous findings. Future

functional studies should yield insight into the biologic relevance of

this locus to the pathways involved in RA.

PMID: 18759306

http://www.ncbi.nlm.nih.gov/pubmed/18759306

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Not an MD