title: Identification of multiple genetic susceptibility loci in Takayasu arteritis.
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)).
authors.affiliation: Department of Physiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul 34093, Turkey.
authors.forename: Güher
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authors.lastname: Saruhan-Direskeneli
authors.forename: Travis
authors.initials: T
authors.lastname: Hughes
authors.forename: Kenan
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authors.lastname: Aksu
authors.forename: Gokhan
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authors.lastname: Keser
authors.forename: Patrick
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authors.forename: Sibel Z
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authors.lastname: Aydin
authors.forename: Fatma
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authors.lastname: Kamalı
authors.forename: Murat
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authors.forename: Gary S
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authors.forename: Servet
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authors.lastname: Onen
authors.forename: Nurullah
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authors.forename: Carol A
authors.initials: CA
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authors.forename: Zeynep
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authors.lastname: Ozbalkan
authors.forename: Askin
authors.initials: A
authors.lastname: Ates
authors.forename: Yasar
authors.initials: Y
authors.lastname: Karaaslan
authors.forename: Kathleen
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authors.lastname: Maksimowicz-McKinnon
authors.forename: Paul A
authors.initials: PA
authors.lastname: Monach
authors.forename: Hüseyin T
authors.initials: HT
authors.lastname: Ozer
authors.forename: Emire
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authors.lastname: Seyahi
authors.forename: Izzet
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authors.lastname: Fresko
authors.forename: Ayse
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authors.lastname: Cefle
authors.forename: Philip
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authors.lastname: Seo
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Warrington
authors.forename: Mehmet A
authors.initials: MA
authors.lastname: Ozturk
authors.forename: Steven R
authors.initials: SR
authors.lastname: Ytterberg
authors.forename: Veli
authors.initials: V
authors.lastname: Cobankara
authors.forename: A Mesut
authors.initials: AM
authors.lastname: Onat
authors.forename: Joel M
authors.initials: JM
authors.lastname: Guthridge
authors.forename: Judith A
authors.initials: JA
authors.lastname: James
authors.forename: Ercan
authors.initials: E
authors.lastname: Tunc
authors.forename: Nurşen
authors.initials: N
authors.lastname: Duzgun
authors.forename: Muge
authors.initials: M
authors.lastname: Bıcakcıgil
authors.forename: Sibel P
authors.initials: SP
authors.lastname: Yentür
authors.forename: Peter A
authors.initials: PA
authors.lastname: Merkel
authors.forename: Haner
authors.initials: H
authors.lastname: Direskeneli
authors.forename: Amr H
authors.initials: AH
authors.lastname: Sawalha
mesh_terms: D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D015235:HLA-B Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains / Q000235:genetics; D059811:HLA-DRB1 Chains / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D053762:Interleukin-12 Subunit p40 / Q000235:genetics; D008297:Male; D009154:Mutation; D009656:North America / Q000453:epidemiology; D017452:Receptors, IgG / Q000235:genetics; D012306:Risk; D013625:Takayasu Arteritis / Q000208:ethnology / Q000235:genetics*; D014421:Turkey / Q000453:epidemiology
chemical_list: C445323:FCGR2A protein, human; C496124:FCGR3A protein, human; D015235:HLA-B Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D059811:HLA-DRB1 Chains; D015395:Histocompatibility Antigens Class I; C500879:IL12B protein, human; D053762:Interleukin-12 Subunit p40; C099187:MHC class I-related chain A; D017452:Receptors, IgG