Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Association of BEND2 with Ankylosing Spondylitis
Uddin1, Mohammed, Rahman1, Proton, Maksymowych2, Walter P., Gladman3, Dafna, Pope1, Angela, Inman4, Robert D.
Ankylosing Spondylitis (AS) is a complex rheumatic disease with a clear genetic predisposition. Pleiotropic genes have been associated with AS including IL-23R and IL-1. As a result we examined the genetic association of 13 nonsynonymous SNPs (nsSNPS) in AS that were identified after a pooled analysis from GWAS of related autoimmune diseases.
In order to generate candidate markers, 1,428 nsSNPs that were common to 5 autoimmune diseases (ankylosing spondylitis, rheumatoid arthritis, type 1 diabetes, autoimmune thyroid disease, and multiple sclerosis) that underwent GWAS by the Welcome Trust Case Control Consortium (WTCCC) were selected. The genotypes were retrieved from the European Genome-Phenome Archive. A pooled analysis involving 6812 UK patients with autoimmune disease and 2952 UK controls was performed. 26 nsSNPs showed a significance of p < 10-3, of which 13 nsSNPs were prioritized for genotyping a cohort of Canadian AS patients. 889 AS cases of Caucasian European ancestry from Canada and 987 controls were genotyped. The patients came from 2 well established AS cohorts: 510 AS cases 502 controls from Alberta and 379 cases and 485 controls from Toronto. The genotyping was done using the Sequenom platform. The Cochran-Amirtage test for trend was performed using the program PLINK.
All samples satisfied the Hardy-Weinberg equilibrium and all SNPs had at least a 92% call rate. In the combined analysis of the Canadian samples nsSNP rs17274127 located on exon 4 of BEN containing domain 2 (BEND2) gene on chromosome Xp22.13 and rs1063588 is located on exon 3 of GCS1 gene at chromosome 2p13.1 achieved statistical significance. For nsSNP rs17274127 of the BEND2 gene the minor allele frequency for the combined population in the cases was 0.170 and in controls was 0.118 (OR 1.56 (1.142.04, p=0.0038). BEND2 is a novel domain in chromatin and DNA viral proteins and mediates protein-DNA and protein-protein interactions during chromatin organization and transcription. For nsSNP rs1063588 of GCS1 gene, the MAF for allele A was 0.183 in the AS cases and 0.153 in the controls (OR 1.24 (1.041.48, p=0.016). GCS1 encodes a GTPase activating protein (GAP) for ADP ribosylation factors that regulate the formation of coated vesicles in intracellular trafficking.
|Population||Gene||rsSNP||Minor Allele||MAF Case||MAF Control||p-value|
A nsSNP within gene BEND2 appears to be associated with AS in the Canadian cohort. Further replication studies are warranted to replicate these findings.
To cite this abstract, please use the following information:
Uddin, Mohammed, Rahman, Proton, Maksymowych, Walter P., Gladman, Dafna, Pope, Angela, Inman, Robert D.; Association of BEND2 with Ankylosing Spondylitis [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1437