RT Journal Article
SR Electronic
T1 Association study of genes related to bone formation and resorption and the extent of radiographic change in ankylosing spondylitis
JF Annals of the Rheumatic Diseases
JO Ann Rheum Dis
FD BMJ Publishing Group Ltd and European League Against Rheumatism
SP 1387
OP 1393
DO 10.1136/annrheumdis-2013-204835
VO 74
IS 7
A1 A Cortes
A1 W P Maksymowych
A1 B P Wordsworth
A1 R D Inman
A1 P Danoy
A1 P Rahman
A1 M A Stone
A1 M Corr
A1 Lianne S Gensler
A1 D Gladman
A1 A Morgan
A1 H Marzo-Ortega
A1 M M Ward
A1 SPARCC (Spondyloarthritis Research Consortium of Canada), TASC (Australo-Anglo-American Spondyloarthritis Consortium)
A1 T J Learch
A1 J D Reveille
A1 M A Brown
A1 M H Weisman
YR 2015
UL http://ard.bmj.com/content/74/7/1387.abstract
AB Objective To identify genetic associations with severity of radiographic damage in ankylosing spondylitis (AS).Method We studied 1537 AS cases of European descent; all fulfilled the modified New York Criteria. Radiographic severity was assessed from digitised lateral radiographs of the cervical and lumbar spine using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). A two-phase genotyping design was used. In phase 1, 498 single nucleotide polymorphisms (SNPs) were genotyped in 688 cases; these were selected to capture >90% of the common haplotypic variation in the exons, exon–intron boundaries, and 5 kb flanking DNA in the 5′ and 3′ UTR of 74 genes involved in anabolic or catabolic bone pathways. In phase 2, 15 SNPs exhibiting p<0.05 were genotyped in a further cohort of 830 AS cases; results were analysed both separately and in combination with the discovery phase data. Association was tested by contingency tables after separating the samples into ‘mild’ and ‘severe’ groups, defined as the bottom and top 40% by mSASSS, adjusted for gender and disease duration.Results Experiment-wise association was observed with the SNP rs8092336 (combined OR 0.32, p=1.2×10−5), which lies within RANK (receptor activator of NFκB), a gene involved in osteoclastogenesis, and in the interaction between T cells and dendritic cells. Association was also found with the SNP rs1236913 in PTGS1 (prostaglandin-endoperoxide synthase 1, cyclooxygenase 1), giving an OR of 0.53 (p=2.6×10−3). There was no observed association between radiographic severity and HLA-B*27.Conclusions These findings support roles for bone resorption and prostaglandins pathways in the osteoproliferative changes in AS.