Genome-wide association study identifies FCGR2A as a susceptibility locus for Kawasaki disease

被引：266

作者：

Khor, Chiea Chuen ^{[2
,3
]}

Davila, Sonia ^{[2
]}

Breunis, Willemijn B. ^{[4
,5
]}

Lee, Yi-Ching

Shimizu, Chisato

Wright, Victoria J. ^{[1
]}

Yeung, Rae S. M. ^{[9
,10
,11
]}

Tan, Dennis E. K.

Sim, Kar Seng

Wang, Jie Jin ^{[12
,13
]}

Wong, Tien Yin ^{[12
,14
,15
]}

Pang, Junxiong ^{[16
]}

Mitchell, Paul ^{[12
]}

Cimaz, Rolando ^{[17
,18
]}

Dahdah, Nagib ^{[19
]}

Cheung, Yiu-Fai ^{[20
]}

Huang, Guo-Ying ^{[21
]}

Yang, Wanling ^{[20
]}

Park, In-Sook ^{[22
]}

Lee, Jong-Keuk ^{[23
]}

Wu, Jer-Yuarn ^{[6
]}

Levin, Michael ^{[1
]}

Burns, Jane C. ^{[7
,8
]}

Burgner, David ^{[24
,25
]}

Kuijpers, Taco W. ^{[4
,5
]}

Hibberd, Martin L. ^{[3
]}

Lau, Yu-Lung ^{[20
]}

Zhang, Jing ^{[20
]}

Ma, Xiao-Jing ^{[21
]}

Liu, Fang ^{[21
]}

Wu, Lin ^{[21
]}

Yoo, Jeong-Jin ^{[26
]}

Hong, Soo-Jong ^{[26
]}

Kim, Kwi-Joo ^{[26
]}

Kim, Jae-Jung ^{[23
]}

Park, Young-Mi ^{[23
]}

Hong, Young Mi ^{[27
]}

Sohn, Sejung ^{[27
]}

Jang, Gi Young ^{[28
]}

Ha, Kee-Soo ^{[28
]}

Nam, Hyo-Kyoung ^{[28
]}

Byeon, Jung-Hye ^{[28
]}

Yun, Sin Weon ^{[29
]}

Han, Myung Ki ^{[30
]}

Lee, Kyung-Yil ^{[31
]}

Hwang, Ja-Young ^{[31
]}

Rhim, Jung-Woo ^{[31
]}

Song, Min Seob ^{[32
]}

Lee, Hyoung-Doo ^{[33
]}

Kim, Dong Soo ^{[34
]}

机构：

[1] Univ London Imperial Coll Sci Technol & Med, Dept Pediat, London, England

[2] Natl Univ Singapore, Genome Inst Singapore, Ctr Mol Epidemiol, Singapore 117548, Singapore

[3] Natl Univ Singapore, Dept Paediat, Fac Med, Singapore 117548, Singapore

[4] Univ Amsterdam, Acad Med Ctr, Dept Pediat Hematol Immunol & Infect Dis, Emma Childrens Hosp, NL-1105 AZ Amsterdam, Netherlands

[5] Univ Amsterdam, Dept Blood Cell Res, Sanquin Res & Landsteiner Lab, Amsterdam, Netherlands

[6] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan

[7] Univ Calif San Diego, Sch Med, Dept Pediat, La Jolla, CA 92093 USA

[8] Rady Childrens Hosp, Dept Pediat, San Diego, CA USA

[9] Univ Toronto, Hosp Sick Children, Dept Pediat, Toronto, ON M5G 1X8, Canada

[10] Univ Toronto, Hosp Sick Children, Dept Immunol, Toronto, ON M5G 1X8, Canada

[11] Univ Toronto, Hosp Sick Children, Dept Med Sci, Toronto, ON M5G 1X8, Canada

[12] Univ Melbourne, Ctr Eye Res Australia, Melbourne, Vic, Australia

[13] Univ Sydney, Ctr Vis Res, Sydney, NSW, Australia

[14] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore 117595, Singapore

[15] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore

[16] Natl Univ Singapore, Dept Epidemiol & Publ Hlth, Fac Med, Singapore 117548, Singapore

[17] Anna Meyer Childrens Hosp, Rheumatol Unit, Florence, Italy

[18] Univ Florence, Dept Pediat, Florence, Italy

[19] Univ Montreal, Div Pediat Cardiol, St Justine Univ Hosp Ctr, Montreal, PQ, Canada

[20] Univ Hong Kong, Dept Paediat & Adolescent Med, Hong Kong, Hong Kong, Peoples R China

[21] Fudan Univ, Pediat Cardiovasc Ctr, Childrens Hosp, Shanghai 200433, Peoples R China

[22] Univ Ulsan, Dept Pediat, Coll Med, Asan Med Ctr, Seoul, South Korea

[23] Univ Ulsan, Asan Inst Life Sci, Coll Med, Seoul, South Korea

[24] Royal Childrens Hosp, Murdoch Childrens Res Inst, Parkville, Vic 3052, Australia

[25] Univ Western Australia, Sch Paediat & Child Hlth, Perth, WA 6009, Australia

[26] Asan Med Ctr, Dept Pediat, Seoul, South Korea

[27] Ewha Womans Univ Hosp, Dept Pediat, Seoul, South Korea

[28] Univ Korea Hosp, Dept Pediat, Seoul, South Korea

[29] Chung Ang Univ Hosp, Dept Pediat, Seoul, South Korea

[30] Univ Ulsan, Dept Pediat, Gangneung Asan Hosp, Kangnung, South Korea

[31] Catholic Univ Korea, Dept Pediat, Daejeon St Marys Hosp, Taejon, South Korea

[32] Inje Univ, Dept Pediat, Paik Hosp, Pusan, South Korea

[33] Pusan Natl Univ Hosp, Dept Pediat, Pusan, South Korea

[34] Yonsei Univ, Coll Med, Dept Pediat, Severance Childrens Hosp, Seoul, South Korea

[35] Seoul Clin Labs, Seoul, South Korea

[36] China Med Univ & Hosp, Dept Pediat, Taichung, Taiwan

[37] Chang Gung Mem Hosp, Dept Pediat, Kaohsiung Med Ctr, Kaohsiung, Taiwan

[38] Mackay Mem Hosp, Dept Pediat, Taipei, Taiwan

[39] Natl Taiwan Univ Hosp, Dept Pediat, Taipei 10016, Taiwan

[40] Chang Gung Mem Hosp, Dept Allergy & Immunol, Kaohsiung Med Ctr, Kaohsiung, Taiwan

[41] Changhua Christian Hosp, Div Pediat Cardiol, Changhua, Taiwan

[42] Changhua Christian Hosp, Dept Pediat, Changhua, Taiwan

[43] Taipei City Hosp, Dept Pediat, Zhongxiao Branch, Taipei, Taiwan

[44] Chang Gung Mem Hosp, Dept Pediat, Linkou, Taiwan

[45] Taipei Vet Gen Hosp, Dept Pediat, Taipei, Taiwan

[46] Univ Western Australia, Sch Pathol & Lab Med, Perth, WA 6009, Australia

[47] PathWest Royal Perth Hosp, Dept Clin Immunol & Immunogenet, Perth, WA, Australia

[48] Womens & Childrens Hosp, SA Pathol, Adelaide, SA, Australia

[49] Univ Adelaide, Sch Paediat & Reprod Hlth, Adelaide, SA, Australia

[50] Royal Childrens Hosp, Parkville, Vic 3052, Australia

来源：

NATURE GENETICS | 2011年 / 43卷 / 12期

基金：

美国国家卫生研究院;

关键词：

COPY NUMBER VARIATION; INTRAVENOUS IMMUNOGLOBULIN; ULCERATIVE-COLITIS; VARIANTS; LINKAGE; POLYMORPHISM; RECEPTORS; GENETICS; DESIGN; POWER;

D O I：

10.1038/ng.981

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Kawasaki disease is a systemic vasculitis of unknown etiology, with clinical observations suggesting a substantial genetic contribution to disease susceptibility. We conducted a genome-wide association study and replication analysis in 2,173 individuals with Kawasaki disease and 9,383 controls from five independent sample collections. Two loci exceeded the formal threshold for genome-wide significance. The first locus is a functional polymorphism in the IgG receptor gene FCGR2A (encoding an H131R substitution) (rs1801274; P = 7.35 x 10(-11), odds ratio (OR) = 1.32), with the A allele (coding for histadine) conferring elevated disease risk. The second locus is at 19q13, (P = 2.51 x 10(-9), OR = 1.42 for the rs2233152 SNP near MIA and RAB4B; P = 1.68 x 10(-12), OR = 1.52 for rs28493229 in ITPKC), which confirms previous findings(1). The involvement of the FCGR2A locus may have implications for understanding immune activation in Kawasaki disease pathogenesis and the mechanism of response to intravenous immunoglobulin, the only proven therapy for this disease.

引用

页码：1241 / 1246

页数：6

共 47 条

[1] The common PPARγ Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes [J].

Altshuler, D ;

Hirschhorn, JN ;

Klannemark, M ;

Lindgren, CM ;

Vohl, MC ;

Nemesh, J ;

Lane, CR ;

Schaffner, SF ;

Bolk, S ;

Brewer, C ;

Tuomi, T ;

Gaudet, D ;

Hudson, TJ ;

Daly, M ;

Groop, L ;

Lander, ES .

NATURE GENETICS, 2000, 26 (01) :76-80

[2] Framework for a fully powered risk engine [J].

不详 .

NATURE GENETICS, 2005, 37 (11) :1153-1153

[3] A genome-wide association study identifies three new susceptibility loci for ulcerative colitis in the Japanese population [J].

Asano, Kouichi ;

Matsushita, Tomonaga ;

Umeno, Junji ;

Hosono, Naoya ;

Takahashi, Atsushi ;

Kawaguchi, Takahisa ;

Matsumoto, Takayuki ;

Matsui, Toshiyuki ;

Kakuta, Yoichi ;

Kinouchi, Yoshitaka ;

Shimosegawa, Tooru ;

Hosokawa, Masayo ;

Arimura, Yoshiaki ;

Shinomura, Yasuhisa ;

Kiyohara, Yutaka ;

Tsunoda, Tatsuhiko ;

Kamatani, Naoyuki ;

Iida, Mitsuo ;

Nakamura, Yusuke ;

Kubo, Michiaki .

NATURE GENETICS, 2009, 41 (12) :1325-U92

[4] Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20 [J].

Bahlo, Melanie ;

Booth, David R. ;

Broadley, Simon A. ;

Brown, Matthew A. ;

Foote, Simon J. ;

Griffiths, Lyn R. ;

Kilpatrick, Trevor J. ;

Lechner-Scott, Jeanette ;

Moscato, Pablo ;

Perreau, Victoria M. ;

Rubio, Justin P. ;

Scott, Rodney J. ;

Stankovich, Jim ;

Stewart, Graeme J. ;

Taylor, Bruce V. ;

Wiley, James ;

Clarke, Glynnis ;

Cox, Mathew B. ;

Csurhes, Peter A. ;

Danoy, Patrick ;

Drysdale, Karen ;

Field, Judith ;

Foote, Simon J. ;

Greer, Judith M. ;

Guru, Preethi ;

Hadler, Johanna ;

McMorran, Brendan J. ;

Jensen, Cathy J. ;

Johnson, Laura J. ;

McCallum, Ruth ;

Merriman, Marilyn ;

Merriman, Tony ;

Pryce, Karen ;

Tajouri, Lotfi ;

Wilkins, Ella J. ;

Browning, Brian L. ;

Browning, Sharon R. ;

Perera, Devindri ;

Butzkueven, Helmut ;

Carroll, William M. ;

Chapman, Caron ;

Kermode, Allan G. ;

Marriott, Mark ;

Mason, Deborah ;

Heard, Robert N. ;

Pender, Michael P. ;

Slee, Mark ;

Tubridy, Niall ;

Willoughby, Ernest .

NATURE GENETICS, 2009, 41 (07) :824-U84

[5] Haploview: analysis and visualization of LD and haplotype maps [J].

Barrett, JC ;

Fry, B ;

Maller, J ;

Daly, MJ .

BIOINFORMATICS, 2005, 21 (02) :263-265

[6] Copy Number Variation at the FCGR Locus Includes FCGR3A, FCGR2C and FCGR3B but not FCGR2A and FCGR2B [J].

Breunis, Willemijn B. ;

van Mirre, Edwin ;

Geissler, Judy ;

Laddach, Nadja ;

Wolbink, Gertjan ;

van der Schoot, Ellen ;

de Haas, Masja ;

de Boer, Martin ;

Roos, Dirk ;

Kuijpers, Taco W. .

HUMAN MUTATION, 2009, 30 (05) :E640-E650

[7] Copy number variation of the activating FCGR2C gene predisposes to idiopathic thrombocytopenic purpura [J].

Breunis, Willernijn B. ;

van Mirre, Edwin ;

Bruin, Marrie ;

Geissler, Judy ;

de Boer, Martin ;

Peters, Marjolein ;

Roos, Dirk ;

de Haas, Masja ;

Koene, Harry R. ;

Kuijpers, Taco W. .

BLOOD, 2008, 111 (03) :1029-1038

[8] Specificity and affinity of human Fcγ receptors and their polymorphic variants for human IgG subclasses [J].

Bruhns, Pierre ;

Iannascoli, Bruno ;

England, Patrick ;

Mancardi, David A. ;

Fernandez, Nadine ;

Jorieux, Sylvie ;

Daeron, Marc .

BLOOD, 2009, 113 (16) :3716-3725

[9] A Genome-Wide Association Study Identifies Novel and Functionally Related Susceptibility Loci for Kawasaki Disease [J].

Burgner, David ;

Davila, Sonia ;

Breunis, Willemijn B. ;

Ng, Sarah B. ;

Li, Yi ;

Bonnard, Carine ;

Ling, Ling ;

Wright, Victoria J. ;

Thalamuthu, Anbupalam ;

Odam, Miranda ;

Shimizu, Chisato ;

Burns, Jane C. ;

Levin, Michael ;

Kuijpers, Taco W. ;

Hibberd, Martin L. .

PLOS GENETICS, 2009, 5 (01)

[10] Infliximab Treatment of Intravenous Immunoglobulin-Resistant Kawasaki Disease [J].

Burns, Jane C. ;

Best, Brookie M. ;

Mejias, Asuncion ;

Mahony, Lynn ;

Fixler, David E. ;

Jafri, Hasan S. ;

Melish, Marian E. ;

Jackson, Mary Anne ;

Asmar, Basim I. ;

Lang, David J. ;

Connor, James D. ;

Capparelli, Edmund V. ;

Keen, Monica L. ;

Mamun, Khalid ;

Keenan, Gregory F. ;

Ramilo, Octavio .

JOURNAL OF PEDIATRICS, 2008, 153 (06) :833-838

← 1 2 3 4 5 →