SUMO4 gene polymorphisms in Chinese Han patients
with Behcet's disease
, Peizeng Yang
, Liping Du
, Hongyan Zhou
, Xiaomin Lin
, Aize Kijlstra
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, PR China
The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, PR China
Eye Research Institute Maastricht, Department of Ophthalmology, University Hospital Maastricht, Maastricht,
Received 7 June 2008; accepted with revision 10 June 2008
Available online 26 July 2008
Abstract Small ubiquitin-like modifier 4 (SUMO4) has been shown to have the potential to
down-regulate NF-κB signal, leading to decreased transcription of pro-inflammatory cytokines.
Recently, SUMO4 polymorphisms have been shown to be associated with several autoimmune
diseases. In the present study, the association of SUMO4 polymorphisms with Behcet's disease
(BD) was investigated. Our results showed a significantly increased frequency of the + 438 C allele
and a significantly decreased frequency of the AGAT haplotype in BD patients (p =0.0002,
corrected p=0.002; p = 0.000015, corrected p = 0.0002, respectively). Stratification analysis
indicated that these significant associations only existed in the HLA-B51 negative subjects
(p=0.004, corrected p=0.032; p = 0.001, corrected p=0.016, respectively). The GGAC haplotype
was negatively associated with HLA-B51 positive BD patients (p=0.0007, corrected p = 0.011). In
conclusion, SUMO4 +438 C allele is associated with susceptibility to BD in HLA-B51 negative
patients, while the AGAT haplotype is protectively associated with BD in HLA-B51 negative
patients. The GGAC haplotype is protectively associated with BD in HLA-B51 positive patients.
© 2008 Elsevier Inc. All rights reserved.
modifier 4 (SUMO4);
Behcet's disease (BD) is a chronic, multi-systemic and inflam-
matory disorder. It is characterized by uveitis, recurrent oral
ulcerations, genital ulcerations and skin lesions. In addition, it
also involves joints, central nervous and gastrointestinal system
. BD exists worldwide, but it is quite common in countries
along the ancient ‘Silk Route’ such as China, Turkey and Japan.
Although the precise etiology and pathogenesis of BD remain
unclear, a widely accepted hypothesis is that the autoimmune
response and genetic factors are both involved in this disease.
HLA-B51 is the strongest indicator for this disease in a variety
of ethnic groups including Iranians, Koreans, Arabs, non-
Ashkenazi Jews and Greeks [2–4]. Additionally, TNF-α, IL-1α,
IL-1β and IL-12 have been demonstrated to be responsible for
susceptibility to BD [5–8]. Small ubiquitin-like modifier 4
(SUMO4), located on 6q25, has been found to be involved in
autoimmune and inflammatory responses through regulation of
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E-mail address: firstname.lastname@example.org (P. Yang).
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Clinical Immunology (2008) 129, 170–175