TY - JOUR
T1 - Identification of multiple genetic susceptibility loci in Takayasu arteritis
AU - Saruhan-Direskeneli, Güher
AU - Hughes, Travis
AU - Aksu, Kenan
AU - Keser, Gokhan
AU - Coit, Patrick
AU - Aydin, Sibel Z.
AU - Alibaz-Oner, Fatma
AU - Kamali, Sevil
AU - Inanc, Murat
AU - Carette, Simon
AU - Hoffman, Gary S.
AU - Akar, Servet
AU - Onen, Fatos
AU - Akkoc, Nurullah
AU - Khalidi, Nader A.
AU - Koening, Curry
AU - Karadag, Omer
AU - Kiraz, Sedat
AU - Langford, Carol A.
AU - McAlear, Carol A.
AU - Ozbalkan, Zeynep
AU - Ates, Askin
AU - Karaaslan, Yasar
AU - Maksimowicz-Mckinnon, Kathleen
AU - Monach, Paul A.
AU - Ozer, Hüseyin T.
AU - Seyahi, Emire
AU - Fresko, Izzet
AU - Cefle, Ayse
AU - Seo, Philip
AU - Warrington, Kenneth J.
AU - Ozturk, Mehmet A.
AU - Ytterberg, Steven R.
AU - Cobankara, Veli
AU - Onat, A. Mesut
AU - Guthridge, Joel M.
AU - James, Judith A.
AU - Tunc, Ercan
AU - Duzgun, Nurşen
AU - Bicakcigil, Muge
AU - Yentür, Sibel P.
AU - Merkel, Peter A.
AU - Direskeneli, Haner
AU - Sawalha, Amr H.
N1 - Funding Information:
This work was supported by funding from the University of Michigan and the Vasculitis Foundation. Procurement and genotyping of the European-American control samples was supported by the National Institutes of Health grants GM103510, AR053483, AI08714, and AI101914. The Vasculitis Clinical Research Consortium has received support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (U54AR057319 and U01 AR51874 04), the National Center for Research Resources (U54 RR019497), and the Office of Rare Diseases Research of the National Center for Advancing Translational Sciences.
PY - 2013/8/8
Y1 - 2013/8/8
N2 - 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).
AB - 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).
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U2 - 10.1016/j.ajhg.2013.05.026
DO - 10.1016/j.ajhg.2013.05.026
M3 - Article
C2 - 23830517
AN - SCOPUS:84881669855
SN - 0002-9297
VL - 93
SP - 298
EP - 305
JO - American journal of human genetics
JF - American journal of human genetics
IS - 2
ER -