Identification of multiple genetic susceptibility loci in Takayasu arteritis

Saruhan-Direskeneli G., HUGHES T., AKSU K., KESER G., COIT P., AYDIN S., ...More

American Journal of Human Genetics, vol.93, no.2, pp.298-305, 2013 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 93 Issue: 2
  • Publication Date: 2013
  • Doi Number: 10.1016/j.ajhg.2013.05.026
  • Journal Name: American Journal of Human Genetics
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.298-305
  • Istanbul University Affiliated: Yes


Takayasu arteritis is a rare inflammatory disease of large arteries. The etiology of Takayasu arteritis remains poorly understood, but genetic contribution to the disease pathogenesis is supported by the genetic association with HLA-B*52. We genotyped ∼200,000 genetic variants in two ethnically divergent Takayasu arteritis cohorts from Turkey and North America by using a custom-designed genotyping platform (Immunochip). Additional genetic variants and the classical HLA alleles were imputed and analyzed. We identified and confirmed two independent susceptibility loci within the HLA region (r 2 < 0.2): HLA-B/MICA (rs12524487, OR = 3.29, p = 5.57 × 10-16) and HLA-DQB1/HLA-DRB1 (rs113452171, OR = 2.34, p = 3.74 × 10-9; and rs189754752, OR = 2.47, p = 4.22 × 10 -9). In addition, we identified and confirmed a genetic association between Takayasu arteritis and the FCGR2A/FCGR3A locus on chromosome 1 (rs10919543, OR = 1.81, p = 5.89 × 10-12). The risk allele in this locus results in increased mRNA expression of FCGR2A. We also established the genetic association between IL12B and Takayasu arteritis (rs56167332, OR = 1.54, p = 2.18 × 10-8). © 2013 The American Society of Human Genetics.