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Open Access Research article

Associations between the HLA-A polymorphism and the clinical manifestations of Behcet's disease

Eun Ha Kang1, Jeong Yeon Kim2, Fujio Takeuchi3, Joon Wan Kim2, Kichul Shin2, Eun Young Lee2, Yun Jong Lee1, Eun Bong Lee24, Myoung Hee Park45 and Yeong Wook Song24*

  • * Corresponding author: Yeong Wook Song ysong@snu.ac.kr

  • † Equal contributors

Author affiliations

1 Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, 166 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, Korea

2 Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, 28 Yeongeon-dong, Jongno-gu, Seoul, Korea

3 Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan

4 Institute of Rheumatology, Medical Research Center, Seoul National University Hospital, 28 Yeongeon-dong, Jongno-gu, Seoul, Korea

5 Department of Laboratory Medicine, Seoul National University Hospital, 28 Yeongeon-dong, Jongno-gu, Seoul, Korea

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Citation and License

Arthritis Research & Therapy 2011, 13:R49  doi:10.1186/ar3292

Published: 24 March 2011

Abstract

Introduction

The objective was to investigate associations between the HLA-A gene and Behcet's disease (BD) and its clinical manifestations.

Methods

Genotyping for the HLA-A locus was performed using the polymerase chain reaction-Luminex typing method in 223 BD patients and 1,398 healthy controls.

Results

The phenotypic frequencies of HLA-A*02:07 (odds ratio (OR) = 2.03, P = 0.002), A*26:01 (OR = 1.85, P = 0.008), and A*30:04 (OR = 2.51, P = 0.006) tended to be higher in BD patients than in normal controls, but the frequency of A*33:03 (OR = 0.59, P = 0.003) tended to be lower in BD patients. A meta-analysis adopting our and the Japanese data confirmed the associations of HLA-A*02:07, A*26:01, and A*33:03 with BD. Furthermore, the frequencies of the HLA-A*02:07, A*26:01, and A*30:04 were significantly higher in patients with skin lesions (OR = 2.37, P < 0.0005, Pc < 0.012) and arthritis (OR = 2.32, P = 0.002, Pc = 0.048), with uveitis (OR = 3.01, P < 0.0005, Pc < 0.012), and with vascular lesions (OR = 9.80, P < 0.0005, Pc < 0.012) and a positive pathergy test (OR = 4.10, P = 0.002, Pc = 0.048), respectively, than in controls. In HLA-B*51 non-carriers, these associations were also significant, being much stronger between HLA-A*26:01 and uveitis (OR = 4.19, P < 0.0005, Pc < 0.012) and between HLA-A*30:04 and vascular lesions (OR = 13.97, P < 0.00005, Pc < 0.0012). In addition, HLA-A*30:04 was associated with genital ulcers in HLA-B*51 non-carriers (OR = 3.89, P = 0.002, Pc = 0.048).

Conclusions

HLA-A*02:07, A*26:01, and A*30:04 were associated with increased risk for BD, while HLA-A*33:03 with decreased risk. HLA-A*02:07, A*26:01, and A*30:04 were associated with skin lesions and arthritis, with uveitis, and with vascular lesions, genital ulcers, and a positive pathergy test, respectively.