Identification of Multiple Genetic Susceptibility Loci in Takayasu Arteritis
Duzgun, Nursen; Saruhan-Direskeneli, Guher; Hughes, Travis; AKSU, KENAN; Sawalha, Amr H.; Direskeneli, Haner; Merkel, Peter A.; Yentur, Sibel P.; Bicakcigil, Muge; Tunc, Ercan; James, Judith A.; Guthridge, Joel M.; Onat, A. Mesut; Cobankara, Veli; Ytterberg, Steven R.; Ozturk, Mehmet A.; Warrington, Kenneth J.; Seo, Philip; ÇEFLE, AYŞE; Fresko, Izzet; Seyahi, Emire; Ozer, Huseyin T.; Monach, Paul A.; Maksimowicz-McKinnon, Kathleen; Karaaslan, Yasar; Ates, Askin; Ozbalkan, Zeynep; McAlear, Carol A.; KESER, GÖKHAN; Coit, Patrick; Aydin, Sibel Z.; ALİBAZ ÖNER, FATMA; Langford, Carol A.; KİRAZ, SEDAT; KARADAĞ, ÖMER; Koening, Curry; Khalidi, Nader A.; AKKOÇ, NURULLAH; ÖNEN, FATOŞ; Akar, Servet; Hoffman, Gary S.; Carette, Simon; Inanc, Murat; Kamali, Sevil
Description:
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)).
Show full item record