Identification Of Multiple Genetic Susceptibility Loci In Takayasu Arteritis
Tarih
2013Yazar
Saruhan-Direskeneli, Guher
Hughes, Travis
Aksu, Kenan
Keser, Gokhan
Coit, Patrick
Aydin, Sibel Z.
Alibaz-Oner, Fatma
Kamali, Sevil
Inanc, Murat
Carette, Simon
Hoffman, Gary S.
Akar, Servet
Onen, Fatos
Akkoc, Nurullah
Khalidi, Nader A.
Koening, Curry
Karadag, Omer
Kiraz, Sedat
Langford, Carol A.
McAlear, Carol A.
Ozbalkan, Zeynep
Ates, Askin
Karaaslan, Yasar
Maksimowicz-McKinnon, Kathleen
Monach, Paul A.
Ozer, Huseyin T.
Seyahi, Emire
Fresko, Izzet
Cefle, Ayse
Seo, Philip
Warrington, Kenneth J.
Ozturk, Mehmet A.
Ytterberg, Steven R.
Cobankara, Veli
Onat, A. Mesut
Guthridge, Joel M.
James, Judith A.
Tunc, Ercan
Duzgun, Nursen
Bicakcigil, Muge
Yentur, Sibel P.
Merkel, Peter A.
Direskeneli, Haner
Sawalha, Amr H.
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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 similar to 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 x 10(-16)) and HLA-DQB1/HLA-DRB1 (rs113452171, OR = 2.34, p = 3.74 x 10(-9); and rs189754752, OR = 2.47, p = 4.22 x 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 x 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 x 10(-8)).