Background/Purpose: Takayasu’s arteritis is a rare inflammatory disease of large arteries. The etiology of Takayasu’s arteritis remains poorly understood, but genetic contribution to the disease pathogenesis is supported by the confirmed genetic association with HLAB*52. Genomic studies in Takayasu’s arteritis have not been previously performed.

Methods: We genotyped ~200,000 genetic variants in two ethnically divergent Takayasu’s arteritis cohorts from Turkey (339 patients and 516 controls) and North America (112 patients and 599 controls) using a custom designed genotyping platform (Immunochip). Additional genetic variants and the classical HLA alleles were imputed and analyzed.

Results: We identified and confirmed two independent susceptibility loci within the HLA region (r²<0.2): HLA-B/MICA (rs12524487, OR= 3.29, P= 5.57X10^-16), and HLADQB1/ HLA-DRB1 (rs113452171, OR= 2.34, P= 3.74X10^-9, and rs189754752, OR=2.47, P= 4.22X10^-9). In addition, we identified and confirmed a novel genetic association between Takayasu’s arteritis and the FCGR2A/FCGR3A locus on chromosome 1 (rs10919543, OR= 1.81, P= 5.89X10^-12). The risk allele in this locus results in increased mRNA expression of FCGR2A. We also established the genetic association between IL12B and Takayasu’s arteritis (rs56167332, OR= 1.54, P= 2.18X10^-8). An association with an additional locus on chromosome 21q22 downstream of PSMG1 did not pass the threshold for genome-wide significance and requires replication (P=4.39X10^-7).

Conclusion: We established multiple genetic susceptibility loci for Takayasu’s arteritis with a genome-wide level of significance including two independent susceptibility loci in the HLA region, and disease susceptibility loci in FCGR2A/FCGR3A and IL12B.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/identification-of-multiple-genetic-susceptibility-loci-in-takayasus-arteritis/