Population differences in SLE susceptibility genes: STAT4 and BLK, but not PXK, are associated with systemic lupus erythematosus in Hong Kong Chinese

被引:89
作者
Yang, W. [1 ]
Ng, P. [1 ]
Zhao, M. [1 ]
Hirankarn, N. [2 ]
Lau, C. S. [3 ]
Mok, C. C. [4 ]
Chan, T. M. [3 ]
Wong, R. W. S. [3 ]
Lee, K. W. [5 ]
Mok, M. Y. [3 ]
Wong, S. N. [6 ]
Avihingsanon, Y. [7 ]
Lee, T. L. [1 ]
Ho, M. H. K. [1 ]
Lee, P. P. W. [1 ]
Wong, W. H. S. [1 ]
Lau, Y. L. [1 ]
机构
[1] Univ Hong Kong, Queen Mary Hosp, Dept Paediat & Adolescent Med, Li Ka Shing Fac Med, Hong Kong, Hong Kong, Peoples R China
[2] Chulalongkorn Univ, Fac Med, Dept Microbiol, Lupus Res Unit, Bangkok 10330, Thailand
[3] Univ Hong Kong, Li Ka Shing Fac Med, Dept Med, Hong Kong, Hong Kong, Peoples R China
[4] Tuen Mun Hosp, Dept Med, Hong Kong, Hong Kong, Peoples R China
[5] Pamela Youde Nethersole Eastern Hosp, Dept Med, Hong Kong, Hong Kong, Peoples R China
[6] Tuen Mun Hosp, Dept Paediat & Adolescent Med, Hong Kong, Hong Kong, Peoples R China
[7] Chulalongkorn Univ, Fac Med, Dept Med, Lupus Res Unit, Bangkok 10330, Thailand
关键词
systemic lupus erythematosus; STAT4; PXK; BLK; population difference; GENOME-WIDE ASSOCIATION; RHEUMATOID-ARTHRITIS; JAPANESE POPULATION; DISEASE; ITGAM; RISK; HAPLOTYPE; VARIANTS;
D O I
10.1038/gene.2009.1
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
In this study, we compared the association of several newly discovered susceptibility genes for systemic lupus erythematosus (SLE) between populations of European origin and two Asian populations. Using 910 SLE patients and 1440 healthy controls from Chinese living in Hong Kong, and 278 SLE patients and 383 controls in Thailand, we studied association of STAT4, BLK and PXK with the disease. Our data confirmed association of STAT4 (rs7574865, odds ratio (OR) 1.71, P = 3.55 x 10(-23)) and BLK (rs13277113, OR = 0.77, P = 1.34 x 10(-5)) with SLE. It was showed that rs7574865 of STAT4 is also linked to hematologic disorders and potentially some other subphenotypes of the disease. More than one genetic variant in STAT4 were found to be associated with the disease independently in our populations (rs7601754, OR = 0.59, P = 1.39 x 10(-9), and P = 0.00034 when controlling the effect of rs7574865). With the same set of samples, however, our study did not detect any significant disease association for PXK, a risk factor for populations of European origin (rs6445975, joint P = 0.36, OR = 1.06, 95% confidence interval: 0.93-1.21). Our study indicates that some of the susceptibility genes for this disease may be population specific. Genes and Immunity (2009) 10, 219-226; doi:10.1038/gene.2009.1; published online 19 February 2009
引用
收藏
页码:219 / 226
页数:8
相关论文
共 22 条
[1]   Haploview: analysis and visualization of LD and haplotype maps [J].
Barrett, JC ;
Fry, B ;
Maller, J ;
Daly, MJ .
BIOINFORMATICS, 2005, 21 (02) :263-265
[2]   Systemic lupus erythematosus-associated defects in the inhibitory receptor FcγRIIb reduce susceptibility to malaria [J].
Clatworthy, Menna R. ;
Willcocks, Lisa ;
Urban, Britta ;
Langhorne, Jean ;
Williams, Tom N. ;
Peshu, Norbert ;
Watkins, Nicholas A. ;
Floto, R. Andres ;
Smith, Kenneth G. C. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (17) :7169-7174
[3]   Epidemiology of systemic lupus erythematosus: a comparison of worldwide disease burden [J].
Danchenko, N ;
Satia, J ;
Anthony, M .
LUPUS, 2006, 15 (05) :308-318
[4]   Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci [J].
Harley, John B. ;
Alarcon-Riquelme, Marta E. ;
Criswell, Lindsey A. ;
Jacob, Chaim O. ;
Kimberly, Robert P. ;
Moser, Kathy L. ;
Tsao, Betty P. ;
Vyse, Timothy J. ;
Langefeld, Carl D. .
NATURE GENETICS, 2008, 40 (02) :204-210
[5]   Genetic susceptibility to SLE is associated with TNF-alpha gene polymorphism-863, but not -308 and -238, in Thai population [J].
Hirankarn, N. ;
Avihingsanon, Y. ;
Wongpiyabovorn, J. .
INTERNATIONAL JOURNAL OF IMMUNOGENETICS, 2007, 34 (06) :425-430
[6]   Association of systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX [J].
Hom, Geoffrey ;
Graham, Robert R. ;
Modrek, Barmak ;
Taylor, Kimberly E. ;
Ortmann, Ward ;
Garnier, Sophie ;
Lee, Annette T. ;
Chung, Sharon A. ;
Ferreira, Ricardo C. ;
Pant, P. V. Krishna ;
Ballinger, Dennis G. ;
Kosoy, Roman ;
Demirci, F. Yesim ;
Kamboh, M. Ilyas ;
Kao, Amy H. ;
Tian, Chao ;
Gunnarsson, Iva ;
Bengtsson, Anders A. ;
Rantapaa-Dahlqvist, Solbritt ;
Petri, Michelle ;
Manzi, Susan ;
Seldin, Michael F. ;
Ronnblom, Lars ;
Syvanen, Ann-Christine ;
Criswell, Lindsey A. ;
Gregersen, Peter K. ;
Behrens, Timothy W. .
NEW ENGLAND JOURNAL OF MEDICINE, 2008, 358 (09) :900-909
[7]   Role of STAT4 polymorphisms in systemic lupus erythematosus in a Japanese population: a case-control association study of the STAT1-STAT4 region [J].
Kawasaki, Aya ;
Ito, Ikue ;
Hikami, Koki ;
Ohashi, Jun ;
Hayashi, Taichi ;
Goto, Daisuke ;
Matsumoto, Isao ;
Ito, Satoshi ;
Tsutsumi, Akito ;
Koga, Minori ;
Arinami, Tadao ;
Graham, Robert R. ;
Hom, Geoffrey ;
Takasaki, Yoshinari ;
Hashimoto, Hiroshi ;
Behrens, Timothy W. ;
Sumida, Takayuki ;
Tsuchiya, Naoyuki .
ARTHRITIS RESEARCH & THERAPY, 2008, 10 (05)
[8]   Association of STAT4 with susceptibility to rheumatoid arthritis and systemic lupus erythematosus in the Japanese population [J].
Kobayashi, Shu ;
Ikari, Katsunori ;
Kaneko, Hirotaka ;
Kochi, Yuta ;
Yamamoto, Kazuhiko ;
Shimane, Kenichi ;
Nakamura, Yusuke ;
Toyama, Yoshiaki ;
Mochizuki, Takeshi ;
Tsukahara, So ;
Kawaguchi, Yasushi ;
Terai, Chihiro ;
Hara, Masako ;
Tomatsu, Taisuke ;
Yamanaka, Hisashi ;
Horiuchi, Takahiko ;
Tao, Kayoko ;
Yasutomo, Koji ;
Hamada, Daisuke ;
Yasui, Natsuo ;
Inoue, Hiroshi ;
Itakura, Mitsuo ;
Okamoto, Hiroshi ;
Kamatani, Naoyuki ;
Momohara, Shigeki .
ARTHRITIS AND RHEUMATISM, 2008, 58 (07) :1940-+
[9]   Variant form of STAT4 is associated with primary Sjogren's syndrome [J].
Korman, B. D. ;
Alba, M. I. ;
Le, J. M. ;
Alevizos, I. ;
Smith, J. A. ;
Nikolov, N. P. ;
Kastner, D. L. ;
Remmers, E. F. ;
Illei, G. G. .
GENES AND IMMUNITY, 2008, 9 (03) :267-270
[10]   Constitutive STAT3 activation in intestinal T cells from patients with Crohn's disease [J].
Lovato, P ;
Brender, C ;
Agnholt, J ;
Kelsen, J ;
Kaltoft, K ;
Svejgaard, A ;
Eriksen, KW ;
Woetmann, A ;
Odum, N .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (19) :16777-16781