Identification of Novel Protein-Coding Genetic Variants Associated with Takayasu Arteritis

Paul Renauer¹, Patrick Coit¹, Peter A. Merkel² and Amr H. Sawalha¹, ¹Division of Rheumatology, University of Michigan, Ann Arbor, MI, ²Penn Vasculitis Center, Division of Rheumatology, University of Pennsylvania, Philadelphia, PA

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: genetics, GWAS, takayasu arteritis and vasculitis

Session Information

Date: Tuesday, November 10, 2015

Title: Vasculitis IV

Session Type: ACR Concurrent Abstract Session

Session Time: 4:30PM-6:00PM

Background/Purpose: Takayasu arteritis is a rare large vessel vasculitis of unclear etiology. Previous studies identified associations between Takayasu arteritis and genetic variants within HLA class I and II, FCGR2A/FCGR3A, IL12B, RPS9/LILRB3, IL6, and chromosome 21q22. The purpose of this study was to uncover protein-coding genetic risk variants in Takayasu arteritis.

Methods: We analyzed 230,050 exonic protein-coding genetic variants included on the Illumina Human Exome BeadChip array in a European-American cohort consisting of 134 patients with Takayasu arteritis and 1051 healthy controls. Genotyping data were subjected to rigorous quality control assessment and filtering prior to genetic analysis.

Results: Outside of the HLA region, 4 nonsynonymous protein-coding variants associated with increased risk for Takayasu arteritis were identified (P<5X10^-5). The most significant genetic associations were with missense genetic variants in TXK (OR= 1.95, P= 7.75X10^-6) and CCDC91 (OR= 3.69, P= 2.11X10^-5). TXK encodes a non-receptor tyrosine kinase that plays an important role in T cell function and differentiation. CCDC91 encodes P56 which interacts with the trans-Golgi network and is involved in regulating protein trafficking. Evidence for gene-gene epistatic interaction was detected between the two genetic variants in TXK and CCDC91 and the risk for Takayasu arteritis (interaction OR= 3.09, P= 2.38X10^-2). Two additional missense variants within the collagen gene COL11A2 and the acyl-coenzyme A synthetase gene ACSM5 were also associated with Takayasu arteritis (P= 3.27X10^-5 and 3.41X10^-5, respectively).

Conclusion: Missense protein-coding variants associated with increased risk for Takayasu arteritis were identified. A larger cohort will be necessary to confirm these associations with a genome-wide level of significance.

Disclosure: P. Renauer, None; P. Coit, None; P. A. Merkel, None; A. H. Sawalha, None.

To cite this abstract in AMA style:

Renauer P, Coit P, Merkel PA, Sawalha AH. Identification of Novel Protein-Coding Genetic Variants Associated with Takayasu Arteritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/identification-of-novel-protein-coding-genetic-variants-associated-with-takayasu-arteritis/. Accessed .

« Back to 2015 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/identification-of-novel-protein-coding-genetic-variants-associated-with-takayasu-arteritis/