Identification of susceptibility loci in IL6, RPS9/LILRB3, and an intergenic locus on chromosome 21q22 in takayasu arteritis in a genome-wide association study

RENAUER, Paul; Saruhan-Direskeneli, Güher; COIT, Patrick; ADLER, Adam; AKSU, KENAN; KESER, GÖKHAN; Alibaz-Oner, Fatma; Aydin, Sibel; Kamali, Sevil; Inanc, Murat; Carette, Simon; CUTHBERTSON, David; HOFFMAN, Gary; Akar, Servet; Onen, Fatos; Akkoc, Nurullah; KHALIDI, Nader; KOENING, Curry; Karadag, Omer; Kiraz, Sedat; LANGFORD, Carol; MAKSIMOWICZ-MCKINNON, Kathleen; McAlear, Carol; OZBALKAN, Zeynep; ATES, Askin; KARAASLAN, Yasar; Duzgun, Nursen; Monach, Paul; Ozer, Huseyin; Erken, Eren; Ozturk, Mehmet; Yazici, Ayten; Cefle, Ayse; Onat, Ahmet; Kisacik, Bunyamin; Pagnoux, Christian; Kasifoglu, Timucin; Seyahi, Emire; Fresko, Izzet; Seo, Philip; Sreih, Antoine; WARRINGTON, Kenneth; YTTERBERG, Steven; Cobankara, Veli; Cunninghame-Graham, Deborah; Vyse, Timothy; Pamuk, Omer; Tunc, S.; Dalkilic, Ediz; Bicakcigil, Muge; Yentur, Sibel; WREN, Jonathan; Merkel, Peter; Direskeneli, Haner; SAWALHA, Amr

doi:10.1002/art.39035

Identification of susceptibility loci in IL6, RPS9/LILRB3, and an intergenic locus on chromosome 21q22 in takayasu arteritis in a genome-wide association study

Atıf İçin Kopyala

RENAUER P. A., Saruhan-Direskeneli G., COIT P., ADLER A., AKSU K., KESER G., ...Daha Fazla

Arthritis and Rheumatology, cilt.67, sa.5, ss.1361-1368, 2015 (SCI-Expanded)

Yayın Türü: Makale / Tam Makale
Cilt numarası: 67 Sayı: 5
Basım Tarihi: 2015
Doi Numarası: 10.1002/art.39035
Dergi Adı: Arthritis and Rheumatology
Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
Sayfa Sayıları: ss.1361-1368
İstanbul Üniversitesi Adresli: Evet

Özet

© 2015, American College of Rheumatology.Objective Takayasu arteritis is a rare large vessel vasculitis with incompletely understood etiology. This study was undertaken to perform the first unbiased genome-wide association analysis of Takayasu arteritis. Methods Two independent cohorts of patients with Takayasu arteritis from Turkey and North America were included in our study. The Turkish cohort consisted of 559 patients and 489 controls, and the North American cohort consisted of 134 patients and 1,047 controls of European ancestry. Genotyping was performed using the Omni1-Quad and Omni2.5 genotyping arrays. Genotyping data were subjected to rigorous quality control measures and subsequently analyzed to discover genetic susceptibility loci for Takayasu arteritis. Results We identified genetic susceptibility loci for Takayasu arteritis with a genome-wide level of significance in IL6 (rs2069837) (odds ratio [OR] 2.07, P = 6.70 × 10^-9), RPS9/LILRB3 (rs11666543) (OR 1.65, P = 2.34 × 10^-8), and an intergenic locus on chromosome 21q22 (rs2836878) (OR 1.79, P = 3.62 × 10^-10). The genetic susceptibility locus in RPS9/LILRB3 lies within the leukocyte receptor complex gene cluster on chromosome 19q13.4, and the disease risk variant in this locus correlates with reduced expression of multiple genes including the inhibitory leukocyte immunoglobulin-like receptor gene LILRB3 (P = 2.29 × 10^-8). In addition, we identified candidate susceptibility genes with suggestive levels of association (P < 1 × 10^-5) with Takayasu arteritis, including PCSK5, LILRA3, PPM1G/NRBP1, and PTK2B. Conclusion Our findings indicate novel genetic susceptibility loci for Takayasu arteritis and uncover potentially important aspects of the pathophysiology of this form of vasculitis.