The chromosome 16q region associated with ankylosing spondylitis includes the candidate gene tumour necrosis factor receptor type 1-associated death domain (TRADD).
OBJECTIVE
To replicate and refine the reported association of ankylosing spondylitis (AS) with two non-synonymous single nucleotide polymorphisms (nsSNPs) on chromosome 16q22.1.


METHODS
Firstly, 730 independent UK patients with AS were genotyped for rs9939768 and rs6979 and allele frequencies were compared with 2879 previously typed historic disease controls. Secondly, the two data sets were combined in meta-analyses. Finally, 5 tagging SNPs, located between rs9939768 and rs6979, were analysed in 1604 cases and 1020 controls.


RESULTS
The association of rs6979 with AS was replicated, p=0.03, OR=1.14 (95% CI 1.01 to 1.28), and a trend for association with rs9939768 detected, p=0.06, OR=1.25 (95% CI 0.99 to 1.57). Meta-analyses revealed association of both SNPs with AS, p=0.0008, OR=1.31 (95% CI 1.12 to 1.54) and p=0.0009, OR=1.15 (95% CI 1.06 to 1.23) for rs9939768 and rs6979, respectively. New associations with rs9033 and rs868213 (p=0.00002, OR=1.23 (95% CI 1.12 to 1.36) and p=0.00002 OR=1.45 (95% CI 1.22 to 1.72), respectively, were identified.


CONCLUSIONS
The region on chromosome 16 that has been replicated in the present work is interesting as the highly plausible candidate gene, tumour necrosis factor receptor type 1 (TNFR1)-associated death domain (TRADD), is located between rs9033 and rs868213. It will require additional work to identify the primary genetic association(s) with AS.
Pointon
Jennifer J
JJ
University of Oxford Institute for Musculoskeletal Sciences, Botnar Research Centre, Oxford OX3 7LD, UK. jenny.pointon@ndorms.ox.ac.uk
Harvey
David
D
Karaderi
Tugce
T
Appleton
Louise H
LH
Farrar
Claire
C
Stone
Millicent A
MA
Sturrock
Roger D
RD
Reveille
John D
JD
Weisman
Michael H
MH
Ward
Michael M
MM
Brown
Matthew A
MA
Wordsworth
B Paul
BP
D016022:Case-Control Studies; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D013167:Spondylitis, Ankylosing / Q000235:genetics*; D053199:TNF Receptor-Associated Death Domain Protein / Q000235:genetics*
D053199:TNF Receptor-Associated Death Domain Protein