Identification of multiple genetic susceptibility loci in Takayasu arteritis

Am J Hum Genet. 2013 Aug 8;93(2):298-305. doi: 10.1016/j.ajhg.2013.05.026. Epub 2013 Jul 3.

Abstract

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)).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Female
  • Genetic Loci*
  • Genetic Predisposition to Disease*
  • Genotyping Techniques
  • HLA-B Antigens / genetics
  • HLA-DQ beta-Chains / genetics
  • HLA-DRB1 Chains / genetics
  • Histocompatibility Antigens Class I / genetics
  • Humans
  • Interleukin-12 Subunit p40 / genetics
  • Male
  • Mutation
  • North America / epidemiology
  • Receptors, IgG / genetics
  • Risk
  • Takayasu Arteritis / ethnology
  • Takayasu Arteritis / genetics*
  • Turkey / epidemiology

Substances

  • FCGR2A protein, human
  • FCGR3A protein, human
  • HLA-B Antigens
  • HLA-DQ beta-Chains
  • HLA-DQB1 antigen
  • HLA-DRB1 Chains
  • Histocompatibility Antigens Class I
  • IL12B protein, human
  • Interleukin-12 Subunit p40
  • MHC class I-related chain A
  • Receptors, IgG