Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
A Putative Functional Variant within the Ubiquitin-Associated Domain-Containing Protein 2 Gene (UBAC2) Is Associated with Increased Risk of Behcet's Disease.
Sawalha7, Amr H., Hughes6, Travis, Nadig6, Ajay, Yilmaz2, Vuslat, Aksu1, Kenan, Keser1, Gokhan, Cefle3, Ayse
Using a genome-wide association scan and DNA pooling, we previously identified 5 novel genetic susceptibility loci for Behcet's disease. Herein, we fine-map the genetic effect within the UBAC2 gene, replicate this genetic association in an independent cohort of Behcet's disease patients and controls, and identify a functional polymorphism in this locus.
Two independent cohorts of Behcet's disease patients and controls from Turkey were studied. The discovery and replication cohorts included 152 patients and 172 controls, and 376 patients and 369 controls, respectively. Genotyping of 14 SNPs within and around UBAC2 was performed using TaqMan SNP genotyping assays.
The genetic association between Behcet's disease and UBAC2 was established and confirmed in two independent cohorts of patients and controls (Meta-analysis OR= 2.05, meta-analysis P= 1.75×10-7). Haplotype analysis identified both a disease risk and a protective haplotype (P= 0.00014 and 0.0075, respectively). Using conditional haplotype analysis we identified that the SNP rs7999348 (A/G) within UBAC2 is the most likely SNP to explain the genetic effect in this locus. Indeed, we demonstrate that rs7999348 is a putative functional SNP that results in increased mRNA expression of a UBAC2 transcript variant in PBMCs of individuals homozygous for the Behcet's disease-associated "G" allele.
We establish and confirm the genetic association between UBAC2 and Behcet's disease in two independent cohorts of patients and controls. Fine mapping of this genetic effect and conditional analysis followed by functional studies identified the minor allele in rs7999348 as a disease-risk allele that alters UBAC2 expression.
To cite this abstract, please use the following information:
Sawalha, Amr H., Hughes, Travis, Nadig, Ajay, Yilmaz, Vuslat, Aksu, Kenan, Keser, Gokhan, et al; A Putative Functional Variant within the Ubiquitin-Associated Domain-Containing Protein 2 Gene (UBAC2) Is Associated with Increased Risk of Behcet's Disease. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :822