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Hwang, Song, Yoo, Song, Kim, Lee, Bae, Choi, Baek, and Kang: Associations between TBX21 Gene Polymorphisms and Korean Patients with Behçet's Disease
Original Article

J Korean Rheum Assoc 2010;17(4):360-367.

Published online: 23 December 2010

DOI: https://doi.org/10.4078/jkra.2010.17.4.360

Associations between TBX21 Gene Polymorphisms and Korean Patients with Behçet's Disease

Jae Hee Hwang1, Ju Kyoung Song1, In Seol Yoo1, Seung Taek Song1, Jin Hyun Kim1, Yun Jong Lee2, Young Deok Bae3, Hyo Jin Choi4, Han Joo Baek4, Seong Wook Kang1

1Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Korea

2Seoul National University College of Medicine, Bundang Hospital, Seongnam, Korea

3Hallym University College of Medicine, Kangdong Sacred Heart Hospital, Seoul, Korea

4Gil Medical Center, Gachon University of Medicine and Science, Incheon, Korea

Received 24 May 201012 July 2010       Accepted 27 July 2010

Copyright © 2010 The Korean Rheumatism Association

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective

Behçet's disease (BD) is a chronic systemic inflammatory disease with unknown etiology. A number of clinical and laboratory findings suggest a strongly polarized Th1 immune response in BD. T-bet is a newly identified Th1 specific T-box transcription factor selectively expressed in Th1 cells. However, it is not yet clear whether the T-bet protein is involved in the proposed Th1-mediated pathogenesis of BD at the transcriptional level. Therefore, this study investigated the potential associations of two single nucleotide polymorphisms (SNPs) at positions -99 (C/G) and -1993 (T/C) in the exon and promoter regions of the TBX21 gene with susceptibility to BD in the Korean population.

Methods

105 patients with BD and 105 healthy controls were studied. All subjects were genotyped using restriction fragment length polymorphism analysis. The genotypes of the two groups were compared with the chi-square or Fisher's exact tests.

Results

The genotypic and allelic distributions of the two SNPs did not differ significantly between the two groups. Furthermore, no associations between the polymorphisms and clinical manifestations were found, except a central nervous system manifestation and arthritis. Furthermore, no associations between the polymorphisms and severity were identified.

Conclusion

TBX21 gene polymorphisms were not associated with susceptibility, clinical manifestations, or severity of BD in the Korean population.

Keywords: TBX21 gene polymorphisms, Behçet's disease

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Fig. 1.
Agarose gel electrophoresis of Eco47III or HhaI digested PCR products. The analysis showed two TBX21- 1993 T/C polymorphic genotypes (A) and three TBX21-99 C/G polymorphic genotypes (B).
jkra-17-360f1.tif
Table 1.
Characteristics of the patients with Behçet's disease (n=105)
Age (year-old) 41.7±1.1
Sex (M : F) 44 (41.9%) : 61 (58.1%)
Mean age of onset (year-old) 31.6±1.1
Mean Disease duration (year) Severity 10.1±0.8
Mild 44 (41.9%)
Moderate 37 (35.2%)
Severe 24 (22.9%)
Recurrent oral ulcer 105 (100%)
Genital ulcer 81 (77.1%)
Uveitis 35 (33.3%)
Skin lesion 95 (90.5%)
Arthritis 32 (30.5%)
Heart involvement 4 (3.8%)
Colonic ulcer 9 (8.6%)
Epididymitis 6 (5.7%)
Central nervous system 5 (5.7%)
Table 2.
The TBX polymorphic alleles and genotypes in patients with Behçet's disease and healthy controls
Controls Patients p-value∗
Allele (n=210 in each group)
TBX-99C/G C 31 (14.8%) 22 (10.5%)
TBX-99C/G G 179 (85.2%) 188 (89.5%) 0.186
TBX-1993T/C C 24 (11.4%) 19 (9.0%)
TBX-1993T/C T 186 (88.6%) 191 (91%) 0.421
Genotype (n=105 in each group)
TBX-99C/G CC 2 (2.0%) 0 (0%) 0.155
TBX-99C/G CG 27 (25.7%) 22 (21.0%) 0.415
TBX-99C/G GG 76 (72.3%) 83 (79.0%) 0.260
TBX-1993T/C CC 0 (0%) 2 (2.0%) 0.155
TBX-1993T/C CT 19 (18.0%) 20 (19.0%) 0.859
TBX-1993T/C TT 86 (82.0%) 83 (79.0%) 0.601

∗Computed by chi-square test with a Bonferroni correction

Table 3.
Associations between polymorphic genotypes and Behçet's disease
Controls Patients p-value∗
Genotype (n=105 in each group)
TBX-99C/G Dominant GG
CG+CC		 84 (80.0%)
21 (20.0%)		 76 (72.4%)
29 (27.6%)		 0.155
TBX-99C/G Recessive CG+GG
CC		 105 (100%)
0 (0%)		 103 (98.1%)
2 (1.9%)		 0.514
TBX-1993T/C Dominant TT
CT+CC		 83 (79%)
22 (21%)		 86 (81.9%)
19 (18.1%)		 0.728
TBX-1993T/C Recessive CT+TT
CC		 103 (98.1%)
2 (1.9%)		 105 (100%)
0 (0%)		 0.498

∗Computed by chi-square test and corrected by Fisher's exact test

Table 4.
Association between TBX alleles and genotypes and severity of Behçet's disease
Mild Moderate Severe p-value∗
Alleles (n=210)
TBX-99
C (n=31)		 14 (45.2%) 10 (32.3%) 7 (22.6%)
TBX-99
G (n=179)		 74 (41.3%) 64 (35.8%) 41 (22.9%) 0.786
TBX-1993
C (n=19)		 6 (31.6%) 7 (36.8%) 6 (31.6%)
TBX-1993
T (n=191)		 82 (42.9%) 67 (35.1%) 42 (22.0%) 0.267
Genotypes (n=105)
TBX-99
CC (n=2)		 1 (50%) 0 (0%) 1 (50%)
TBX-99
CG (n=27)		 12 (44.4%) 10 (37.0%) 5 (18.5%)
TBX-99
GG (n=76)		 31 (40.7%) 27 (35.5%) 18 (23.6%) 0.784
TBX-1993
CC (n=0)		 0 (0%) 0 (0%) 0 (0%)
TBX-1993
CT (n=19)		 6 (31.5%) 7 (36.8%) 6 (31.5%)
TBX-1993
TT (n=86)		 38 (44.1%) 30 (34.8%) 18 (20.9%) 0.243

∗Computed by chi-square test and linear-by-linear association

Table 5.
Association between TBX alleles and arthritis in patients with Behçet's disease
TBX-99C/G TBX-1993T/C
Allele No. Allele No.
Arthritis C 9 (14.1%) C 2 (3.1%)
G 55 (85.9%) T 62 (96.9%)∗

∗p=0.048, odds ratio (95% confidence interval)=0.245 (0.055~1.093)

Table 6.
Association between TBX genotypes with arthritis and central nervous system involvement in patients with Behçet's disease
TBX-99C/G TBX-1993T/C
Genotype No. Genotype No.
Arthritis CC 0 (0%) CC 0 (0%)
CG 9 (28.1%) CT 2 (6.2%)∗
GG 23 (71.9%) TT 30 (93.8%)∗
CNS involvement CC 1 (16.7%)† CC 0 (0%)
CG 0 (0%) CT 2 (33.3%)
GG 5 (83.3%) TT 4 (66.7%)

∗p=0.037, odds ratio (OR) (95% confidence interval [CI])=4.554 (0.985~21.05), †p=0.006, OR (95% CI)=19.60 (1.064~361.2)

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