Identification of Multiple Genetic Susceptibility Loci in Takayasu Arteritis
Makaleler > Tam Makale · 2013
Yazarlar: Guher Saruhan-Direskeneli, Travis HUGHES, Kenan AKSU, Gökhan KESER, Patrick COIT, SEMA AYDIN, Fatma Alibaz-Oner, Sevil Kamali, Murat Inanc, Simon Carette, Gary S. HOFFMAN, Servet Akar, Fatos Onen, Nurullah Akkoc, Nader A. Khalidi, Curry KOENING, Omer Karadag, Sedat Kiraz, Carol A. LANGFORD, Carol A. McAlear, Zeynep OZBALKAN, Askin ATES, Yasar KARAASLAN, Kathleen MAKSIMOWICZ-MCKINNON, Paul A. Monach, Huseyin T. Ozer, Emire Seyahi, Izzet Fresko, Ayse Cefle, Philip Seo, Kenneth J. WARRINGTON, Mehmet A. Ozturk, Steven R. YTTERBERG, Veli Cobankara, A. Mesut Onat, Joel M. GUTHRIDGE, Judith A. JAMES, Ercan Tunc, Nursen DUZGUN, Muge Bicakcigil, Sibel P. Yentur, Peter A. Merkel, Suzan GÜVEN, Amr H. SAWALHA
The American Journal of Human Genetics, SCI Expanded İndekslerine Giren Dergi, Uluslararası, Wos, 2013, cilt 93, ss 298-305
DOI: 10.1016/j.ajhg.2013.05.026
Özet
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)).