Elsevier

Human Immunology

Volume 71, Issue 10, October 2010, Pages 988-991
Human Immunology

Interleukin-17 gene polymorphism is associated with Vogt–Koyanagi–Harada syndrome but not with Behçet's disease in a Chinese Han population

https://doi.org/10.1016/j.humimm.2010.06.020Get rights and content

Abstract

Interleukin (IL)–17 has been shown to play an important role in certain autoimmune diseases. The present study was performed to investigate the association of IL-17A and IL-17F gene polymorphisms with two autoimmune uveitis entities, Vogt–Koyanagi–Harada (VKH) syndrome and Behçet's disease (BD), in a Chinese Han population. A total of 362 BD patients, 385 VKH syndrome patients, and 412 controls were genotyped for IL-17A/rs2275913 and IL-17F/rs763780 using polymerase chain reaction–restricted fragment length polymorphism. The result showed that the genotype and allele distribution of the two single nucleotide polymorphisms (SNPs) in all subjects were in Hardy–Weinberg equilibrium. A significantly decreased frequency of IL-17F/rs763780 C allele (p = 0.006, pc = 0.036) and an increased frequency of TT genotype (p = 0.005, pc = 0.030) were observed in VKH patients compared with normal controls. There was no association of the tested two SNPs with BD, even after adjusting gender ratio. Stratification analysis failed to find any association of extraocular manifestations of two uveitis entities and the tested two SNPs. The C allele and TT genotype of rs763780 in the IL-17F gene appear to be associated with protection and susceptibility to VKH syndrome. The tested two IL-17 SNPs are not found to be associated with Behçet's disease.

Introduction

Vogt–Koyanagi–Harada (VKH) syndrome and Behçet's disease (BD) are the two most common uveitis entities seen in China [1]. VKH syndrome is an autoimmune disorder characterized by granulomatous panuveitis, pleocytosis, dysacusis, alopecia, poliosis, and vitiligo [2]. BD is another autoimmune disease with multisystem involvement. It is characterized by recurrent uveitis, oral ulcers, genital ulcers, and skin lesions [3]. It is generally recognized that both diseases are induced by a complicated interaction of several factors, such as genetic background, autoimmune response, environmental factors, and other exogenous elements [4], [5], [6], [7]. Concerning gene susceptibility to both diseases, a number of studies have revealed that human leukocyte antigen (HLA) genes are the most potent risk genes associated with their development [8], [9], [10]. Studies on the association of the non-HLA gene for these two diseases, such as the tyrosinase family, interferon-γ (IFN-γ), protein-tyrosine-phosphatase nonreceptor 22 gene (PTPN22), and killer cell immunoglobulin-like receptors (KIR) gene in Japanese patients with VKH syndrome [11], [12], [13], [14], [15], the cytotoxic T lymphocyte antigen–4 (CTLA-4) gene in Chinese patients with VKH syndrome [16], and interleukin-8 (IL-8) in Korean patients with BD have been reported [17]. However, the identified risk genes cannot fully explain the genetic background for these two diseases.

IL-17 is a relatively novel cytokine family, which consists of six members: interleukin (IL)–17A (also previously known as IL-17), IL-17B, IL-17C, IL-17D, IL-17E, and IL-17F [18]. IL-17A and IL-17F have been shown to play an important role in the pathogenesis of certain autoimmune diseases [19], [20], [21], [22]. The polymorphisms of both IL-17A and IL-17F have shown to be associated with a number of autoimmune or immune diseases, including asthma, rheumatoid arthritis, inflammatory bowel disease, and chronic fatigue syndrome [23], [24], [25], [26], [27]. In our recent studies we found that the upregulation of IL-17 was associated with intraocular inflammation in VKH and BD patients [28], [29]. In view of the previously mentioned facts, we speculated that IL-17 polymorphisms might be involved in the susceptibility to VKH syndrome and BD. The study was therefore designed to examine whether IL-17A and IL-17F polymorphisms were associated with these two autoimmune uveitis entities.

Section snippets

Study population

The study group comprised 747 patients (385 VKH syndrome patients and 362 BD patients) of Chinese Han origin. All the VKH syndrome patients and BD patients were consecutively diagnosed at the Zhongshan Ophthalmic Center, Sun Yat-sen University or the First Affiliated Hospital of Chongqing Medical University, P. R. China between April 2005 and October 2009. The diagnosis for VKH syndrome was strictly based on the criteria of First International Workshop [30]. A total of 348 patients were

Results

Two SNPs of IL-17 were successfully genotyped in 362 BD patients, 385 VKH patients, and 412 normal controls.* The clinical findings of BD and VKH syndrome are summarized in Table 2. As there was an excessive proportion of male to female in the tested BD patients, a gender ratio adjustment was performed to avoid the bias caused by gender unbalance. No differences were observed in the distribution of age and gender ratio between VKH patients and controls (Table 3). The genotype and allele

Discussion

In this study, we attempted to detect the association of two SNPs of IL-17A and IL-17F with two uveitis entities, VKH and BD, in a Chinese Han population. It was found that the frequency of TT genotype of rs763780 was positively associated with VKH syndrome, whereas the frequency of C allele was negatively linked to this disease. In regard to BD, there was no association between this disease and the tested two SNPs of IL-17.

VKH syndrome and BD are two of the most common uveitis entities in

Acknowledgments

This work was supported by Key Project of Natural Science Foundation (30630064), National Supporting Project of P. R. China (2007BAI18B10), Natural Science Foundation Major International (Regional) Joint Research Project (30910103912), National Natural Science Foundation Project (30973242), Program for the Training of a Hundred Outstanding S&T Leaders of Chongqing Municipality, Key Project of Health Bureau of Chongqing (2008-1-15), Project of Medical Science and Technology of Chongqing (

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