Dataset Information

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

ABSTRACT: 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 NF?B), 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.

SUBMITTER: Cortes A

PROVIDER: S-EPMC4470170 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Cortes A A Maksymowych W P WP Wordsworth B P BP Inman R D RD Danoy P P Rahman P P Stone M A MA Corr M M Gensler Lianne S LS Gladman D D Morgan A A Marzo-Ortega H H Ward M M MM Learch T J TJ Reveille J D JD Brown M A MA Weisman M H MH

Annals of the rheumatic diseases 20140320 7

<h4>Objective</h4>To identify genetic associations with severity of radiographic damage in ankylosing spondylitis (AS).<h4>Method</h4>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 ...[more]

PMID: 24651623

Similar Datasets

Project description:To study the effect of tumor necrosis factor ? (TNF?) inhibitors on progressive spinal damage in patients with ankylosing spondylitis (AS).All AS patients meeting the modified New York criteria who had been monitored prospectively and had at least 2 sets of spinal radiographs a minimum of 1.5 years apart were included in the study (n=334). The patients received standard therapy, which included nonsteroidal antiinflammatory drugs and TNF? inhibitors. Radiographic severity was assessed by the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Patients with a rate of AS progression that was ?1 mSASSS unit/year were considered progressors. Univariable and multivariable regression analyses were done. Propensity score matching and sensitivity analysis were performed. A zero-inflated negative binomial (ZINB) model was used to analyze the effect of TNF? inhibitors on the change in the mSASSS with varying followup periods. Potential confounders, such as disease activity (as assessed by the Bath Ankylosing Spondylitis Disease Activity Index), the erythrocyte sedimentation rate, C-reactive protein level, HLA-B27 positivity, sex, age at onset, smoking burden (number of pack-years), and baseline damage, were included in the model.TNF? inhibitor treatment was associated with a 50% reduction in the odds of progression, with an odds ratio (OR) of 0.52 (95% confidence interval [95% CI] 0.30-0.88, P=0.02). Patients with a delay of >10 years in starting therapy were more likely to experience progression as compared to those who started earlier (OR 2.4 [95% CI 1.09-5.3], P=0.03). In the ZINB model, the use of TNF? inhibitors significantly reduced disease progression when the gap between radiographs was >3.9 years. The protective effect of TNF? inhibitors was stronger after propensity score matching.Treatment with TNF? inhibitors appears to reduce radiographic progression in AS patients, especially with early initiation and with longer duration of followup.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets