Identification of Susceptibility Loci in IL6, RPS9/LILRB3, and an Intergenic Locus on Chromosome 21q22 in Takayasu Arteritis in a Genome-Wide Association Study

被引：91

作者：

Renauer, Paul A. ^{[1
]}

Saruhan-Direskeneli, Guher ^{[2
]}

Coit, Patrick ^{[1
]}

Adler, Adam ^{[3
]}

Aksu, Kenan ^{[4
]}

Keser, Gokhan ^{[4
]}

Alibaz-Oner, Fatma ^{[5
]}

Aydin, Sibel Z. ^{[6
]}

Kamali, Sevil ^{[2
]}

Inanc, Murat ^{[2
]}

Carette, Simon ^{[7
]}

Cuthbertson, David ^{[8
]}

Hoffman, Gary S. ^{[9
]}

Akar, Servet ^{[10
,11
]}

Onen, Fatos ^{[12
]}

Akkoc, Nurullah ^{[12
]}

Khalidi, Nader A. ^{[13
,14
]}

Koening, Curry ^{[15
]}

Karadag, Omer ^{[16
]}

Kiraz, Sedat ^{[16
]}

Langford, Carol A. ^{[9
]}

Maksimowicz-McKinnon, Kathleen ^{[17
,18
]}

McAlear, Carol A. ^{[19
]}

Ozbalkan, Zeynep ^{[20
]}

Ates, Askin ^{[20
,21
]}

Karaaslan, Yasar ^{[20
,22
]}

Duzgun, Nursen ^{[21
]}

Monach, Paul A. ^{[23
]}

Ozer, Huseyin T. E. ^{[24
]}

Erken, Eren ^{[24
]}

Ozturk, Mehmet A. ^{[25
]}

Yazici, Ayten ^{[26
]}

Cefle, Ayse ^{[26
]}

Onat, Ahmet Mesut ^{[27
]}

Kisacik, Bunyamin ^{[27
]}

Pagnoux, Christian ^{[7
]}

Kasifoglu, Timucin ^{[28
]}

Seyahi, Emire ^{[2
]}

Fresko, Izzet ^{[2
]}

Seo, Philip ^{[29
]}

Sreih, Antoine G. ^{[19
]}

Warrington, Kenneth J. ^{[30
]}

Ytterberg, Steven R. ^{[30
]}

Cobankara, Veli ^{[31
]}

Cunninghame-Graham, Deborah S. ^{[32
]}

Vyse, Timothy J. ^{[32
]}

Pamuk, Omer N. ^{[33
]}

Tunc, S. Ercan ^{[34
]}

Dalkilic, Ediz ^{[35
]}

Bicakcigil, Muge ^{[36
]}

机构：

[1] Univ Michigan, Ann Arbor, MI 48109 USA

[2] Istanbul Univ, Istanbul, Turkey

[3] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA

[4] Ege Univ, Izmir, Turkey

[5] Marmara Univ, Istanbul, Turkey

[6] Koc Univ, Istanbul, Turkey

[7] Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada

[8] Univ S Florida, Tampa, FL USA

[9] Cleveland Clin Fdn, Cleveland, OH 44195 USA

[10] Dokuz Eylul Univ, Izmir, Turkey

[11] Katip Celebi Univ, Izmir, Turkey

[12] Dokuz Eylul Univ, Izmir, Turkey

[13] St Josephs Healthcare, Hamilton, ON, Canada

[14] McMaster Univ, Hamilton, ON, Canada

[15] Univ Utah, Salt Lake City, UT USA

[16] Hacettepe Univ, Ankara, Turkey

[17] Univ Pittsburgh, Pittsburgh, PA USA

[18] Henry Ford Hlth Syst, Detroit, MI USA

[19] Univ Penn, Philadelphia, PA 19104 USA

[20] Ankara Numune Training & Res Hosp, Ankara, Turkey

[21] Ankara Univ, TR-06100 Ankara, Turkey

[22] Hitit Univ, Corum, Turkey

[23] Boston Univ, Sch Med, Boston, MA 02118 USA

[24] Cukurova Univ, Adana, Turkey

[25] Gazi Univ, Ankara, Turkey

[26] Kocaeli Univ, Kocaeli, Turkey

[27] Gaziantep Univ, Gaziantep, Turkey

[28] Eskisehir Osmangazi Univ, Eskisehir, Turkey

[29] Johns Hopkins Univ, Baltimore, MD USA

[30] Mayo Clin, Coll Med, Rochester, MN USA

[31] Pamukkale Univ, Denizli, Turkey

[32] Kings Coll London, London WC2R 2LS, England

[33] Trakya Univ, Edirne, Turkey

[34] Suleyman Demirel Univ, TR-32200 Isparta, Turkey

[35] Uludag Univ, Bursa, Turkey

[36] Yeditepe Univ, Istanbul, Turkey

[37] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA

[38] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA

来源：

ARTHRITIS & RHEUMATOLOGY | 2015年 / 67卷 / 05期

关键词：

ANKYLOSING-SPONDYLITIS; TURKEY; CLASSIFICATION; VISUALIZATION; POPULATION; DISEASE;

D O I：

10.1002/art.39035

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 x 10(-9)), RPS9/LILRB3 (rs11666543) (OR 1.65, P = 2.34 x 10(-8)), and an intergenic locus on chromosome 21q22 (rs2836878) (OR 1.79, P = 3.62 x 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 x 10(-8)). In addition, we identified candidate susceptibility genes with suggestive levels of association (P < 1 x 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.

引用

页码：1361 / 1368

页数：8

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