Association study of genes related to bone formation and resorption and the extent of radiographic change in ankylosing spondylitis

Objective To identify genetic associationswith 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 SpondylitisSpinal 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 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.