Mar 24, 2011 - and the clinical manifestations of Behcet's disease ... was to investigate associations between the HLA-A gene and Behcet's disease (BD).
Kang et al. Arthritis Research & Therapy 2011, 13:R49 http://arthritis-research.com/content/13/2/R49
RESEARCH ARTICLE
Open Access
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 Lee2,4, Myoung Hee Park4,5 and Yeong Wook Song2,4*
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 1.0)
A*24:03
0
(0.0)
1
(0.1)
NA
0
(0.0)
1
(0.1)
NA
0
(0.0)
0
(0.0)
A*24:04
0
(0.0)
1
(0.1)
NA
0
(0.0)
1
(0.1)
NA
0
(0.0)
0
(0.0)
NA
A*24:08
0
(0.0)
1
(0.1)
NA
0
(0.0)
1
(0.1)
NA
0
(0.0)
0
(0.0)
NA
A*24:20
1
(0.5)
2
(0.1)
3.14 (0.28 to 34.82)
1
(0.7)
2
(0.2)
3.95 (0.36 to 43.84)
0
(0.0)
0
(0.0)
NA
A*26:01
26
(11.7)
93
(6.7)
1.85 (1.17 to 2.93)
19
(13.4)
74
(6.6)
2.18 (1.27 to 3.72)
7
(8.6)
19
(6.7)
1.31 (0.53 to 3.23)
A*26:02
11
(4.9)
58
(4.2)
1.20 (0.62 to 2.32)
7
(4.9)
46
(4.1)
1.21 (0.53 to 2.73)
4
(4.9)
12
(4.3)
1.17 (0.37 to 3.72)
A*26:03
7
(3.1)
17
(1.2)
2.63 (1.08 to 6.42)
5
(3.5)
14
(1.3)
2.87 (1.02 to 8.10)
2
(2.5)
3
(1.1)
2.35 (0.39 to 14.34)
0.008 (0.24)
0.037 (> 1.0)
0.004 (0.12)
0.053
P (Pc)
0
(0.0)
1
(0.1)
NA
0
(0.0)
0
(0.0)
NA
0
(0.0)
1
(0.4)
NA
0 2
(0.0) (0.9)
1 28
(0.1) (2.0)
0 2
(0.0) (1.4)
1 24
(0.1) (2.2)
(0.0) (0.0)
0 4
(0.0) (1.4)
NA NA
1
(0.5)
0
(0.0)
1
(0.7)
0
(0.0)
NA 0.65 (0.15 to 2.78) NA
0 0
A*29:02
NA 0.44 (0.10 to 1.87) NA
0
(0.0)
0
(0.0)
NA
0.031 (> 1.0)
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A*26:05 A*26:18 A*29:01
0.035 (> 1.0)
Kang et al. Arthritis Research & Therapy 2011, 13:R49 http://arthritis-research.com/content/13/2/R49
Table 2 Distribution of phenotypic frequencies of HLA-A alleles
A*30:01
8
(3.6)
74
(5.3)
0.67 (0.32 to 1.40)
A*30:04
12
(5.4)
31
(2.2)
2.51 (1.27 to 4.96)
A*31:01
22
(9.9)
160
(11.4)
A*31:11
0
(0.0)
1
A*32:01 A*33:03
0 43
(0.0) (19.3)
26 405
A*68:01
1
(0.5)
3
(0.2)
2.09 (0.22 to 20.23)
7
(4.9)
63
(5.7)
0.87 (0.39 to 1.93)
11
(7.8)
26
(2.3)
3.52 (1.70 to 7.29)
0.85 (0.53 to 1.35)
10
(7.0)
98
(8.8)
(0.1)
NA
0
(0.0)
0
(1.9) (29.0)
NA 0.59 (0.41 to 0.83)
0 33
(0.0) (23.2)†
25 345
1
(0.7)
2
(0.2)
0.006 (0.18)
0.003 (0.09)
1
(1.2)
11
(3.9)
0.31 (0.04 to 2.42)
1
(1.2)
5
(1.8)
0.69 (0.08 to 6.01)
0.79 (0.40 to 1.55)
12
(14.8)
62
(22.0)
0.62 (0.31 to 1.21)
(0.0)
NA
0
(0.0)
1
(0.4)
NA
(2.2) (30.9)
NA 0.68 (0.45 to 1.02)
0 10
(0.0) (12.4)
1 60
(0.4) (21.3)
NA 0.52 (0.25 to 1.07)
3.95 (0.36 to 43.85)
0
(0.0)
1
(0.4)
NA
0.002 (0.06)
Kang et al. Arthritis Research & Therapy 2011, 13:R49 http://arthritis-research.com/content/13/2/R49
Table 2 Distribution of phenotypic frequencies of HLA-A alleles (Continued)
Values are presented as N (%). P (Pc) values are presented for those alleles with estimable OR (95% CI) and P-values of < 0.05. †P = 0.047 (HLA-B*51 negative vs. positive patients). BD, Behcet’s disease; CI, confidence intervals; NA, not applicable; OR, odds ratio; Pc, corrected P.
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Kang et al. Arthritis Research & Therapy 2011, 13:R49 http://arthritis-research.com/content/13/2/R49
Page 6 of 9
Table 3 Meta-analysis on the association between HLA-A alleles and BD† Allele
HLA-B*51 non-carriers
Total subjects OR (95% CI)
P
I2 (%)
A*01:01
0.54 (0.21 to 1.42)
0.21
76
0.04
92.7
A*02:01
1.20 (0.97 to 1.48)
0.09
0
0.70
65.7
A*02:03
0.96 (0.35 to 2.65)
0.93
27
0.24
67.5
0.99 (0.32 to 3.09)
0.99
0
0.47
70.9
A*02:06
0.86 (0.66 to 1.13)
0.28
0
0.69
58.2
0.73 (0.50 to 1.06)
0.10
0
0.62
60.7
A*02:07
1.96 (1.34 to 2.85)
0.0005
0
0.62
66.6
2.00 (1.30 to 3.09)
0.002
0
0.69
69.7
A*02:10
0.37 (0.06 to 2.37)
0.30
0
0.43
80.0
0.37 (0.05 to 3.05)
0.36
0
0.72
74.5
A*03:01
0.44 (0.15 to 1.26)
0.13
0
0.56
71.1
0.77 (0.26 to 2.21)
0.62
0
0.84
75.7
A*03:02 A*11:01
0.71 (0.12 to 4.21) 0.78 (0.60 to 1.03)
0.70 0.08
0 77
0.56 0.04
52.4 50.5
1.12 (0.18 to 6.77) 0.85 (0.61 to 1.19)
0.90 0.35
0 51
0.64 0.15
51.9 50.6
A*11:02
1.30 (0.30 to 5.57)
0.73
75
0.05
18.0
1.23 (0.20 to 7.71)
0.82
57
0.13
11.5
A*24:02
0.89 (0.75 to 1.05)
0.18
44
0.18
47.0
0.83 (0.67 to 1.03)
0.10
0
0.43
48.8
A*24:20
0.60 (0.13 to 2.83)
0.52
59
0.12
12.1
0.68 (0.12 to 3.73)
0.65
63
0.10
12.6
A*26:01
1.89 (1.41 to 2.53)
