Lack of association between polymorphisms in interlukin (IL)-12,
IL-12R, IL-23, IL-23R genes and Takayasu arteritis in a Chinese
population
Supplementary Information
•
Table S1. Haplotype analysis between polymorphisms in IL12A, IL12B, IL12RB1,
IL12RB2, IL23R and TA risk.
•
Table S2. Associations of polymorphisms in IL12A, IL12B, IL12RB1, IL12RB2,
and IL23R with TA onset age.
•
P14-16
Table S7. Frequencies of SNPs in IL12A, IL12B, IL12RB1, IL12RB2, and IL23R
in HLA-B*52-positive TA patients and controls.
•
P11-13
Table S6. Associations of polymorphisms in IL12A, IL12B, IL12RB1, IL12RB2,
and IL23R with TA severity.
•
P8-10
Table S5. Associations of polymorphisms in IL12A, IL12B, IL12RB1, IL12RB2,
and IL23R with TA refractoriness.
•
P5-7
Table S4. Associations of polymorphisms in IL12A, IL12B, IL12RB1, IL12RB2,
and IL23R with TA progression.
•
P2-4
Table S3. Associations of polymorphisms in IL12A, IL12B, IL12RB1, IL12RB2,
and IL23R with TA aortic regurgitation.
•
P1
P17-18
Table S8. Frequencies of SNPs in IL12A, IL12B, IL12RB1, IL12RB2, and IL23R
in HLA-B*52-positive and HLA-B*52-negative TA patients.
P19-20
Table S1. Haplotype analysis between polymorphisms in IL12A, IL12B, IL12RB1,
IL12RB2, IL23R and TA risk.
Gene
IL12A
IL12B
IL12RB1
IL23R
Haplotype
Frequency (%)
OR (95% CI)
P-value P’
Patients
Controls
69.6
22.0
8.3
68.1
23.3
8.6
1.0 (ref)
0.93 (0.66,1.32)
0.95 (0.57,1.59)
0.70
0.84
53.1
38.9
48.6
43.7
1.0 (ref)
0.81 (0.61,1.09)
0.17
G-GC
7.6
7.7
rs6871626- rs56167332
C-C
65.6
68.6
A-A
34.4
31.2
rs11575934- rs393548
T-T
64.8
63.7
C-T
21.0
23.6
C-A
14.1
11.9
rs11209032- rs6677188- rs1495965
A-T-G
52.8
49.5
G-T-A
27.1
26.3
G-A-A
18.0
22.2
G-T-G
1.7
1.9
*
**
P < 0.05, P < 0.01; P’, after Bonferroni correction.
0.92 (0.53,1.59)
0.77
1.0 (ref)
1.15 (0.85,1.55)
0.36
1.0 (ref)
0.86 (0.61,1.23)
1.18 (0.77,1.80)
0.41
0.44
1.0 (ref)
0.96 (0.69,1.35)
0.77 (0.53,1.12)
0.88 (0.30,2.57)
0.83
0.16
0.81
rs2243115- rs582054
T-A
T-T
G-T
rs2546890- rs17860508
G- TTAGAG
A-GC
1
Table S2-1. Associations of SNPs in IL12A, IL12B, IL12RB1, IL12RB2,
with TA onset age.
Gene
SNP
TA onset age
OR (95% CI)
≤20 years (n) >20 years (n)
IL12A
rs2243115
G/T
7/85
17/179
0.87 (0.35,2.17)
GG+GT/TT
7/39
16/82
0.92 (0.35,2.42)
rs568408
A/G
9/83
24/172
0.75 (0.32,1.78)
AA+AG/GG
9/37
24/74
0.75 (0.32,1.78)
rs582054
T/A
24/68
63/131
0.73 (0.42,1.28)
TT+TA/AA
20/26
54/43
0.61 (0.30,1.24)
IL12B
rs3212227
C/A
41/51
101/95
0.75 (0.45,1.25)
CC+CA/AA
32/14
76/22
0.66 (0.30,1.45)
rs6887695
C/G
39/53
96/100
0.77 (0.47,1.27)
CC+CG/GG
30/16
72/26
0.68 (0.32,1.44)
rs6871626
A/C
29/63
70/126
0.82 (0.48,1.41)
AA+AC/CC
25/21
58/40
0.82 (0.41,1.66)
rs56167332
A/C
29/63
70/126
0.82 (0.48,1.41)
AA+AC/CC
25/21
58/40
0.82 (0.40,1.66)
rs2546890
A/G
39/53
74/122
1.24 (0.73,2.14)
AA+AG/GG
32/14
63/35
1.27 (0.60,2.69)
rs17860508
GC(G)/TTAGAG(T) 46/46
88/108
1.25 (0.74,2.11)
GG+GT/TT
36/10
70/28
1.44 (0.63,3.29)
IL12RB1 rs393548
A/T
13/79
28/168
0.99 (0.49,2.00)
AA+AT/TT
13/33
25/73
1.15 (0.52,2.53)
rs11575934
C/T
35/57
66/130
1.21 (0.72,2.02)
CC+CT/TT
30/16
53/45
1.59 (0.77,3.29)
IL12RB2 rs3790567
A/G
28/64
47/149
1.47 (0.80,2.68)
AA+AG/GG
25/21
44/54
1.46 (0.72,2.95)
rs12131065
A/G
40/52
73/123
1.26 (0.78,2.04)
AA+AG/GG
31/15
56/42
1.55 (0.74,3.23)
IL23R
rs10889677
2
and IL23R
P-value
0.76
0.87
0.51
0.51
0.27
0.17
0.27
0.30
0.31
0.31
0.48
0.58
0.48
0.58
0.42
0.53
0.40
0.39
0.97
0.73
0.47
0.21
0.21
0.29
0.34
0.24
P’
C/A
29/63
48/148
CC+CA/AA
24/22
42/56
rs1004819
C/T
40/52
68/128
CC+CT/TT
31/15
56/42
rs11209032
G/A
53/39
83/113
GG+GA/AA
38/8
64/34
rs1495965
A/G
51/41
79/117
AA+AG/GG
38/8
62/36
rs6677188
A/T
18/74
35/161
AA+AT/TT
18/28
34/64
*
**
P < 0.05, P < 0.01; P’, after Bonferroni correction.
3
1.41 (0.82,2.43) 0.22
1.46 (0.72,2.94) 0.30
1.44 (0.87,2.39) 0.16
1.55 (0.74,3.23) 0.24
1.81 (1.10,3.00) 0.02*
2.52 (1.06,6.01) 0.04*
0.36
0.66
1.84 (1.11,3.08) 0.02*
2.76 (1.16,6.56) 0.02*
0.34
0.39
1.15 (0.57,2.31) 0.70
1.21 (0.59,2.50) 0.61
Table S2-2. Associations of haplotypes in IL12A, IL12B, IL12RB1, IL12RB2, and
IL23R with TA onset age.
Gene
IL12A
IL12B
IL12RB1
IL23R
Haplotype
Frequency (%)
OR (95% CI)
P-value
≤20 years
>20 years
73.9
16.3
9.8
67.2
20.5
12.2
1.0 (ref)
0.73 (0.38,1.41)
0.73 (0.32,1.65)
0.35
0.45
48.9
41.3
55.1
37.7
1.0 (ref)
1.23 (0.73,2.08)
0.43
G-GC
8.7
7.2
rs6871626- rs56167332
C-C
68.5
64.3
A-A
31.5
35.7
rs11575934- rs393548
T-T
62.0
66.3
C-T
23.9
19.4
C-A
14.1
14.3
rs11209032- rs6677188- rs1495965
A-T-G
42.4
57.7
G-T-A
36.2
23.0
G-A-A
19.2
17.3
G-T-G
1.9
1.5
*
**
P < 0.05, P < 0.01; P’, after Bonferroni correction.
1.37 (0.54,3.50)
0.51
1.0 (ref)
0.83 (0.49,1.41)
0.49
1.0 (ref)
1.32 (0.72,2.43)
1.06 (0.51,2.19)
0.37
0.88
rs582054- rs568408
A-G
T-G
T-A
rs2546890- rs17860508
G- TTAGAG
A-GC
4
1.0 (ref)
2.13 (1.19,3.79) 0.10
1.53 (0.78,3.02) 0.21
1.93 (0.31,12.00) 0.47
P’
Gene
IL12A
IL12B
Table S3-1. Associations of SNPs in IL12A, IL12B,
with TA aortic regurgitation.
SNP
TA aortic regurgitation (AR)
Severe AR (n) Mild AR (n)
rs2243115
G/T
0/10
10/92
GG+GT/TT
0/5
10/41
rs568408
A/G
0/10
12/90
AA+AG/GG
0/5
12/39
rs582054
T/A
2/8
34/66
TT+TA/AA
2/3
29/21
rs3212227
A/C
AA+AC/CC
rs6887695
G/C
GG+GC/CC
rs6871626
A/C
AA+AC/CC
rs56167332
A/C
AA+AC/CC
rs2546890
A/G
AA+AG/GG
rs17860508
GC(G)/TTAGAG(T)
GG+GT/TT
IL12RB1 rs393548
A/T
AA+AT/TT
rs11575934
C/T
CC+CT/TT
IL12RB2 rs3790567
A/G
AA+AG/GG
rs12131065
A/G
AA+AG/GG
IL12RB1, IL12RB2, and IL23R
OR (95% CI)
P-value P’
-
1.00
1.00
-
1.00
1.00
0.46 (0.09,2.42)
0.48 (0.07,3.15)
0.36
0.45
6/4
4/1
44/58
36/15
2.12 (0.52,8.68)
1.67(0.17,16.17)
0.29
0.66
6/4
4/1
49/53
36/15
1.55 (0.44,5.50)
1.67(0.17,16.17)
0.50
0.66
3/7
3/2
40/62
33/18
0.64 (0.15,2.80)
0.82 (0.13,5.36)
0.55
0.83
3/7
3/2
40/62
33/18
0.64 (0.15,2.80)
0.82 (0.13,5.36)
0.55
0.83
6/4
4/1
33/69
28/23
3.18(0.80,12.66)
3.29(0.34,31.48)
0.10
0.30
6/4
4/1
39/63
33/18
2.67(0.64,11.13)
2.18(0.23,21.02)
0.18
0.50
1/9
1/4
14/88
13/38
0.70 (0.08,5.96)
0.73 (0.07,7.15)
0.74
0.79
2/8
2/3
33/69
28/23
0.51 (0.10,2.62)
0.55 (0.08,3.56)
0.42
0.53
2/8
2/3
29/73
24/27
0.64 (0.13,3.11)
0.75 (0.12,4.88)
0.58
0.76
2/8
2/3
42/60
28/23
0.47 (0.12,1.90)
0.55 (0.08,3.56)
0.29
0.53
5
IL23R
rs10889677
C/A
1/9
27/75
CC+CA/AA
1/4
25/26
rs1004819
C/T
4/6
40/62
CC+CT/TT
2/3
33/18
rs11209032
G/A
4/6
51/51
GG+GA/AA
2/3
38/13
rs1495965
A/G
4/6
48/54
AA+AG/GG
2/3
36/15
rs6677188
A/T
2/8
21/81
AA+AT/TT
2/3
20/31
*
**
P < 0.05, P < 0.01; P’, after Bonferroni correction.
6
0.27 (0.03,2.41)
0.26 (0.03,2.49)
0.24
0.24
1.03 (0.28,3.82)
0.36 (0.06,2.38)
0.96
0.29
0.69 (0.20,2.45)
0.23 (0.03,1.52)
0.57
0.13
0.78 (0.22,2.69)
0.28 (0.04,1.84)
0.69
0.18
0.96 (0.17,5.54)
1.03 (0.16,6.74)
0.96
0.97
Table S3-2. Associations of haplotypes in IL12A, IL12B, IL12RB1, IL12RB2, and
IL23R with TA aortic regurgitation.
Gene
Haplotype
Frequency (%)
Severe AR
IL12B
P-value P’
1.0 (ref)
2.91(0.77,11.05)
-
0.11
-
1.0 (ref)
0.66 (0.16,2.72)
0.57
Mild AR
rs2546890- rs17860508
G- TTAGAG
39.9
60.7
A-GC
59.9
31.3
G-GC
0.1
6.9
rs6871626- rs56167332
C-C
70.0
60.8
A-A
30.0
39.2
*
**
P < 0.05, P < 0.01; P’, after Bonferroni correction.
7
OR (95% CI)
Gene
IL12A
IL12B
IL12RB1
IL12RB2
IL23R
Table S4-1. Associations of SNPs in IL12A, IL12B, IL12RB1, IL12RB2, and IL23R
with TA progression.
SNP
TA progression
OR (95% CI)
P-value P’
progressive (n) non- progressive (n)
rs2243115
G/T
4/42
20/222
1.06 (0.34,3.25)
0.92
GG+GT/TT
4/19
19/102
1.13 (0.35,3.69)
0.84
rs568408
A/G
5/41
28/214
0.92 (0.31,2.71)
0.88
AA+AG/GG
5/18
28/93
0.92 (0.31,2.71)
0.88
rs582054
T/A
12/34
75/165
0.77 (0.38,1.59)
0.49
TT+TA/AA
11/12
63/57
0.83 (0.34,2.02)
0.68
rs3212227
A/C
23/23
119/123
1.04 (0.55,1.96)
0.92
AA+AC/CC
16/7
92/29
0.72 (0.27,1.92)
0.51
rs6887695
C/G
23/23
112/130
1.16 (0.62,2.15)
0.65
CC+CG/GG
16/7
86/35
0.93 (0.35,2.46)
0.88
rs6871626
A/C
15/31
84/158
0.91 (0.46,1.79)
0.78
AA+AC/CC
12/11
71/50
0.77 (0.31,1.88)
0.56
rs56167332
A/C
15/31
84/158
0.91 (0.46,1.79)
0.78
AA+AC/CC
12/11
71/50
0.77 (0.31,1.88)
0.56
rs2546890
A/G
17/29
96/146
0.88 (0.44,1.76)
0.71
AA+AG/GG
14/9
81/40
0.77 (0.31,1.93)
0.57
rs17860508
GC(G)/TTAGAG(T) 22/24
112/130
1.07 (0.55,2.07)
0.84
GG+GT/TT
17/6
89/32
1.02 (0.37,2.81)
0.97
rs393548
A/T
4/42
37/205
0.53 (0.18,1.57)
0.25
AA+AT/TT
4/19
34/87
0.54 (0.17,1.70)
0.29
rs11575934
C/T
17/29
84/158
1.10 (0.57,2.11)
0.77
CC+CT/TT
14/9
69/52
1.17 (0.47,2.92)
0.73
rs3790567
A/G
10/36
65/177
0.73 (0.32,1.63)
0.44
AA+AG/GG
10/13
59/62
0.81 (0.33,1.99)
0.64
rs12131065
A/G
14/32
99/143
0.66 (0.34,1.26)
0.21
AA+AG/GG
13/10
74/47
0.83 (0.34,2.04)
0.68
rs10889677
8
C/A
19/27
58/184
CC+CA/AA
16/7
50/71
rs1004819
C/T
25/21
83/159
CC+CT/TT
19/4
68/53
rs11209032
G/A
29/17
107/135
GG+GA/AA
19/4
83/38
rs1495965
A/G
27/19
103/139
AA+AG/GG
19/4
81/40
rs6677188
A/T
11/35
42/200
AA+AT/TT
11/12
41/80
*
**
P < 0.05, P < 0.01; P’, after Bonferroni correction.
9
2.22 (1.14,4.35)
3.25 (1.24,8.47)
0.02*
0.02*
0.35
0.29
2.28 (1.19,4.39)
3.70 (1.19,11.53)
0.01*
0.02*
0.24
0.43
2.10 (1.10,4.02)
2.18 (0.69,6.83)
0.03*
0.18
0.50
1.00
1.91 (1.00,3.65)
2.35 (0.75,7.36)
0.05
0.14
0.89
1.00
1.67 (0.70,3.93)
1.79 (0.73,4.40)
0.25
0.21
Table S4-2. Associations of haplotypes in IL12A, IL12B, IL12RB1, IL12RB2, and
IL23R with TA progression.
Frequency (%)
progressive nonprogressive
OR (95% CI)
P-value P’
73.9
15.2
10.9
68.5
19.9
11.6
1.0 (ref)
0.71 (0.30,1.71)
0.87 (0.31,2.42)
0.45
0.79
52.1
53.3
1.0 (ref)
36.9
10.9
39.2
7.1
0.96 (0.49,1.89)
1.58 (0.53,4.69)
0.91
0.41
67.4
32.6
65.3
34.7
1.0 (ref)
0.91 (0.47,1.78)
0.78
63.0
28.3
8.7
65.3
19.4
15.3
1.0 (ref)
1.51 (0.73,3.13)
0.59 (0.20,1.78)
0.27
0.34
A-T-G
37.0
55.8
G-T-A
34.8
25.7
G-A-A
23.9
16.8
G-T-G
4.3
1.1
*
**
P < 0.05, P < 0.01; P’, after Bonferroni correction.
1.0 (ref)
2.05 (0.97,4.32)
2.13 (0.92,4.91)
5.29(0.83,33.97)
0.06
0.07
0.05
Gene
Haplotype
IL12A
rs582054- rs568408
A-G
T-G
T-A
rs2546890- rs17860508
G- TTAGAG
IL12B
IL12RB1
IL23R
A-GC
G-GC
rs6871626- rs56167332
C-C
A-A
rs11575934- rs393548
T-T
C-T
C-A
rs11209032- rs6677188- rs1495965
10
0.21
Gene
IL12A
IL12B
IL12RB1
IL12RB2
IL23R
Table S5-1. Associations of SNPs in IL12A, IL12B, IL12RB1, IL12RB2, and IL23R
with TA refractoriness.
SNP
TA refractoriness
OR (95% CI)
P-value
refractory (n)
non- refractory (n)
rs2243115
G/T
4/40
20/224
1.12 (0.36,3.45)
0.84
GG+GT/TT
4/18
19/103
1.21 (0.37,4.00)
0.76
rs568408
A/G
2/42
31/213
0.29 (0.06,1.33)
0.11
AA+AG/GG
2/20
31/91
0.29 (0.06,1.33)
0.11
rs582054
T/A
7/37
80/162
0.38 (0.16,0.89)
0.03*
TT+TA/AA
6/16
68/53
0.29 (0.11,0.80)
0.02*
rs3212227
C/A
23/21
119/125
1.16 (0.60,2.22)
0.66
CC+CA/AA
18/4
90/32
1.60 (0.50,5.08)
0.43
rs6887695
C/G
21/23
114/130
1.04 (0.55,1.95)
0.90
CC+CG/GG
15/7
87/35
0.86 (0.32,2.30)
0.77
rs6871626
A/C
15/29
84/160
0.98 (0.50,1.96)
0.97
AA+AC/CC
12/10
71/51
0.86 (0.35,2.15)
0.75
rs56167332
A/C
15/29
84/160
0.98 (0.50,1.96)
0.97
AA+AC/CC
12/10
71/51
0.86 (0.35,2.15)
0.75
rs2546890
A/G
18/26
95/149
1.10 (0.55,2.21)
0.79
AA+AG/GG
15/7
80/42
1.13 (0.43,2.97)
0.81
rs17860508
GC(G)/TTAGAG(T) 20/24
114/130
0.95 (0.48,1.86)
0.87
GG+GT/TT
15/7
91/31
0.73 (0.27,1.96)
0.53
rs393548
A/T
11/33
30/214
2.41 (1.08,5.40)
0.03*
AA+AT/TT
9/13
29/93
2.22 (0.86,5.72)
0.10
rs11575934
C/T
22/22
79/165
2.10 (1.08,4.09)
0.03*
CC+CT/TT
15/7
68/54
1.70 (0.65,4.47)
0.28
rs3790567
A/G
11/33
64/180
0.93 (0.42,2.05)
0.85
AA+AG/GG
11/11
58/64
1.10 (0.45,2.74)
0.83
rs12131065
A/G
13/31
100/144
0.63 (0.32,1.23)
0.18
AA+AG/GG
10/12
77/45
0.49 (0.19,1.22)
0.12
rs10889677
11
P’
0.49
0.30
0.59
0.51
C/A
6/38
71/173
CC+CA/AA
6/16
60/62
rs1004819
C/T
10/34
98/146
CC+CT/TT
9/13
78/44
rs11209032
G/A
15/29
121/123
GG+GA/AA
12/10
90/32
rs1495965
A/G
14/30
116/128
AA+AG/GG
11/11
89/33
rs6677188
A/T
8/36
45/199
AA+AT/TT
8/14
44/78
*
**
P < 0.05, P < 0.01; P’, after Bonferroni correction.
12
0.39 (0.16,0.96)
0.39 (0.16,1.06)
0.04*
0.06
0.74
0.44 (0.21,0.94)
0.39 (0.15,0.99)
0.03*
0.05
0.61
0.84
0.54 (0.28,1.05)
0.43 (0.17,1.08)
0.07
0.07
0.52 (0.26,1.03)
0.37 (0.15,0.94)
0.06
0.04*
0.98 (0.39,2.45)
1.01 (0.39,2.60)
0.96
0.98
0.64
Table S5-2. Associations of haplotypes in IL12A, IL12B, IL12RB1, IL12RB2, and
IL23R with TA refractoriness.
Frequency (%)
refractory
nonrefractory
OR (95% CI)
P-value P’
84.1
11.4
4.5
66.7
20.6
12.7
1.0 (ref)
0.44 (0.16,1.18)
0.28 (0.07,1.24)
0.10
0.08
54.5
52.8
1.0 (ref)
40.9
4.6
38.5
8.2
1.03 (0.53,2.00)
0.54 (0.12,2.45)
0.93
0.42
65.9
34.1
65.6
34.4
1.0 (ref)
0.99 (0.50,1.94)
0.97
50.0
25.0
25.0
67.6
20.1
12.3
1.0 (ref)
1.68 (0.76,3.71)
2.75 (1.21,6.25)
0.19
0.013*
A-T-G
65.9
50.4
G-T-A
15.9
29.2
G-A-A
15.9
18.3
G-T-G
0.0
1.9
*
**
P < 0.05, P < 0.01; P’, after Bonferroni correction.
1.0 (ref)
0.42 (0.17,1.00)
0.66 (0.27,1.61)
-
0.05
0.36
-
Gene
Haplotype
IL12A
rs582054- rs568408
A-G
T-G
T-A
rs2546890- rs17860508
G- TTAGAG
IL12B
IL12RB1
IL23R
A-GC
G-GC
rs6871626- rs56167332
C-C
A-A
rs11575934- rs393548
T-T
C-T
C-A
rs11209032- rs6677188- rs1495965
13
0.052
Table S6-1. Associations of SNPs in IL12A, IL12B, IL12RB1, IL12RB2, and IL23R
with TA severity.
Gene
SNP
TA refractoriness
OR (95% CI)
P-value P’
severe (n) mild (n)
IL12A
rs2243115
G/T
11/111
13/153
1.17 (0.50,2.70)
0.72
GG+GT/TT
11/50
12/71
1.30 (0.53,3.18)
0.56
rs568408
A/G
8/114
25/141
0.35 (0.14,0.84)
0.02*
0.35
*
AA+AG/GG
8/53
25/58
0.35 (0.14,0.84)
0.02
0.35
rs582054
T/A
28/94
59/105
0.52 (0.30,0.90)
0.02*
0.35
**
TT+TA/AA
23/38
51/31
0.37 (0.19,0.73)
0.0041
0.075
IL12B
rs3212227
C/A
59/63
83/83
0.93 (0.58,1.50)
0.78
CC+CA/AA
46/15
62/21
1.04 (0.48,2.23)
0.92
rs6887695
C/G
57/65
78/88
0.99 (0.62,1.57)
0.96
CC+CG/GG
42/19
60/23
0.85 (0.41,1.75)
0.65
rs6871626
A/C
42/80
57/109
1.00 (0.61,1.66)
0.99
AA+AC/CC
35/26
48/35
0.98 (0.50,1.92)
0.96
rs56167332
A/C
42/80
57/109
1.00 (0.61,1.66)
0.99
AA+AC/CC
35/26
48/35
0.98 (0.50,1.92)
0.96
rs2546890
A/G
47/75
66/100
0.94 (0.57,1.57)
0.82
AA+AG/GG
40/21
55/28
0.97 (0.48,1.95)
0.93
rs17860508
GC(G)/TTAGAG(T) 55/67
79/87
0.90 (0.55,1.46)
0.66
GG+GT/TT
44/17
62/21
0.88 (0.42,1.85)
0.73
IL12RB1 rs393548
A/T
22/100
19/147
1.71 (0.87,3.34)
0.12
AA+AT/TT
20/41
18/65
1.76 (0.83,3.72)
0.14
rs11575934
C/T
51/71
50/116
1.67 (1.02,2.75)
0.04
CC+CT/TT
40/21
43/40
1.77 (0.90,3.50)
0.10
IL12RB2 rs3790567
A/G
35/87
40/126
1.32 (0.74,2.34)
0.35
AA+AG/GG
32/29
37/46
1.37 (0.71,2.66)
0.35
rs12131065
A/G
48/74
65/101
1.01 (0.64,1.59)
0.98
AA+AG/GG
37/24
50/33
1.02 (0.52,2.00)
0.96
IL23R
rs10889677
14
C/A
31/91
46/120
CC+CA/AA
27/34
39/44
rs1004819
C/T
44/78
64/102
CC+CT/TT
35/26
52/31
rs11209032
G/A
58/64
78/88
GG+GA/AA
44/17
58/25
rs1495965
A/G
56/66
74/92
AA+AG/GG
43/18
57/26
rs6677188
A/T
23/99
30/136
AA+AT/TT
23/38
29/54
*
**
P < 0.05, P < 0.01; P’, after Bonferroni correction.
15
0.89 (0.53,1.51)
0.90 (0.46,1.74)
0.67
0.75
0.90 (0.56,1.46)
0.80 (0.41,1.58)
0.67
0.52
1.02 (0.65,1.61)
1.12 (0.54,2.32)
0.93
0.77
1.05 (0.66,1.68)
1.09 (0.53,2.24)
0.83
0.82
1.07 (0.55,2.07)
1.13 (0.57,2.24)
0.85
0.73
Table S6-2. Associations of haplotypes in IL12A, IL12B, IL12RB1, IL12RB2, and
IL23R genes with TA severity.
Frequency (%)
severe
mild
Gene
Haplotype
IL12A
rs582054- rs568408
A-G
77.0
63.7
T-G
16.4
21.2
T-A
6.6
15.1
rs2546890- rs17860508
G- TTAGAG
54.1
52.4
A-GC
37.7
39.7
G-GC
7.4
7.9
rs6871626- rs56167332
C-C
65.6
65.7
A-A
34.4
34.3
rs11575934- rs393548
T-T
58.2
69.9
C-T
23.8
18.7
C-A
18.0
11.4
rs11209032- rs6677188- rs1495965
A-T-G
52.5
53.0
G-T-A
27.9
26.7
G-A-A
18.0
17.9
G-T-G
0.8
2.2
*
**
P < 0.05, P < 0.01; P’, after Bonferroni correction.
IL12B
IL12RB1
IL23R
16
OR (95% CI)
P-value
P’
1.0 (ref)
0.64 (0.35,1.18)
0.37 (0.16,0.87)
0.15
0.019*
0.075
1.0 (ref)
0.92 (0.56,1.51)
0.91 (0.37,2.26)
0.74
0.84
1.0 (ref)
1.00 (0.61,1.64)
0.99
1.0 (ref)
1.53 (0.85,2.75)
1.89 (0.96,3.74)
0.16
0.06
1.0 (ref)
1.06 (0.61,1.84)
1.01 (0.53,1.91)
0.34 (0.04,3.15)
0.83
0.98
0.32
Gene
IL12A
IL12B
IL12RB1
IL12RB2
IL23R
Table S7. Frequencies of SNPs in IL12A, IL12B, IL12RB1,
HLA-B*52-positive TA patients and controls.
SNP
HLA-B*52-positive
TA patients (n) Normal controls (n)
rs2243115
G/T
4/68
2/26
GG+GT/TT
4/32
2/12
rs568408
A/G
6/66
1/27
AA+AG/GG
6/30
1/13
rs582054
T/A
16/56
7/21
TT+TA/AA
12/24
6/8
rs3212227
C/A
31/41
11/17
CC+CA/AA
24/12
8/6
rs6887695
C/G
30/42
12/16
CC+CG/GG
24/12
9/5
rs6871626
A/C
22/50
7/21
AA+AC/CC
20/16
7/7
rs56167332
A/C
22/50
7/21
AA+AC/CC
20/16
7/7
rs2546890
A/G
33/39
10/18
AA+AG/GG
27/9
7/7
rs17860508
TTAGAG(T)/GC(G) 35/37
14/14
TT+TG/GG
26/10
10/4
rs393548
A/T
10/62
2/26
AA+AT/TT
9/27
2/12
rs11575934
C/T
25/47
7/21
CC+CT/TT
22/14
7/7
rs3790567
A/G
14/58
6/22
AA+AG/GG
14/22
5/9
rs12131065
A/G
26/46
10/18
AA+AG/GG
20/16
9/5
rs10889677
17
IL12RB2, and IL23R in
OR (95% CI)
P-value P’
0.75 (0.12,4.64)
0.75 (0.12,4.64)
0.76
0.76
2.6 (0.28,23.81)
2.6 (0.28,23.81)
0.40
0.40
0.89 (0.36,2.19)
0.67 (0.19,2.36)
0.79
0.53
1.15 (0.49,2.70)
1.50 (0.42,5.32)
0.74
0.53
0.95 (0.40,2.29)
1.11 (0.30,4.05)
0.91
0.87
1.42 (0.47,4.32)
1.25 (0.36,4.31)
0.54
0.72
1.42 (0.47,4.32)
1.25 (0.36,4.31)
0.54
0.72
1.54 (0.61,3.88)
3.00 (0.83,10.91)
0.36
0.095
0.95 (0.41,2.20)
1.04 (0.26,4.09)
0.90
0.96
2.04 (0.42,9.83)
2.00 (0.37,10.69)
0.37
0.42
1.78 (0.60,5.34)
1.57 (0.45,5.45)
0.30
0.48
0.87 (0.27,2.76)
1.15 (0.32,4.13)
0.81
0.84
1.02 (0.42,2.48)
0.69 (0.19,2.49)
0.97
0.58
C/A
17/55
9/19
CC+CA/AA
16/20
9/5
rs1004819
C/T
27/45
14/14
CC+CT/TT
22/14
13/1
rs11209032
A/G
38/34
9/19
AA+AG/GG
30/6
9/5
rs1495965
G/A
39/33
10/18
GG+GA/AA
30/6
10/4
rs6677188
A/T
12/60
9/19
AA+AT/TT
12/24
8/6
*
**
P < 0.05, P < 0.01; P’, after Bonferroni correction.
18
0.56 (0.18,1.76)
0.44 (0.12,1.59)
0.32
0.21
0.52 (0.19,1.45)
0.12 (0.01,1.03)
0.21
0.053
3.33 (1.06,10.51)
2.78 (0.68,11.28)
0.04*
0.15
2.84 (0.93,8.66)
2.00 (0.47,8.56)
0.06
0.35
0.34 (0.11,1.11)
0.38 (0.11,1.33)
0.07
0.13
0.72
Table S8. Frequencies of SNPs in IL12A, IL12B, IL12RB1, IL12RB2, and IL23R in
HLA-B*52-positive and HLA-B*52-negative TA patients.
Gene
SNP
TA patients
OR (95% CI)
P-value P’
HLA-B*52- HLA-B*52positive (n) negative (n)
IL12A
rs2243115
G/T
4/68
20/196
0.58 (0.19,1.75) 0.33
GG+GT/TT
4/32
19/89
0.59 (0.19,1.85) 0.36
rs568408
A/G
6/66
27/189
0.60 (0.23,1.60) 0.31
AA+AG/GG
6/30
27/81
0.60 (0.23,1.60) 0.31
rs582054
T/A
16/56
71/143
0.57 (0.30,1.08) 0.08
TT+TA/AA
12/24
62/45
0.36 (0.16,0.80) 0.012*
0.22
IL12B
rs3212227
C/A
31/41
111/105
0.71 (0.41,1.23) 0.22
CC+CA/AA
24/12
84/24
0.57 (0.25,1.31) 0.19
rs6887695
C/G
30/42
105/111
0.76 (0.45,1.30) 0.32
CC+CG/GG
24/12
78/30
0.77 (0.34,1.73) 0.53
rs6871626
A/C
22/50
77/139
0.79 (0.44,1.41) 0.42
AA+AC/CC
20/16
63/45
0.89 (0.42,1.91) 0.77
rs56167332
A/C
22/50
77/139
0.79 (0.44,1.41) 0.42
AA+AC/CC
20/16
63/45
0.89 (0.42,1.91) 0.77
rs2546890
A/G
33/39
80/136
1.52 (0.85,2.73) 0.16
AA+AG/GG
27/9
68/40
1.77 (0.75,4.13) 0.19
rs17860508
GC(G)/TTAGAG(T) 37/35
97/119
1.33 (0.76,2.34) 0.32
GG +GT/TT
27/9
79/29
1.10 (0.46,2.62) 0.83
IL12RB1 rs393548
A/T
10/62
31/185
0.96 (0.45,2.07) 0.92
AA+AT/TT
9/27
29/79
0.91 (0.38,2.16) 0.83
rs11575934
C/T
25/47
76/140
0.98 (0.56,1.71) 0.94
CC+CT/TT
22/14
61/47
1.21 (0.56,2.62) 0.63
IL12RB2 rs3790567
A/G
14/58
61/155
0.57 (0.28,1.15) 0.12
AA+AG/GG
14/22
55/53
0.61 (0.28,1.32) 0.21
rs12131065
A/G
26/46
87/129
0.85 (0.50,1.44) 0.55
AA+AG/GG
20/16
67/41
0.76 (0.36,1.64) 0.49
19
IL23R
rs10889677
C/A
17/55
60/156
CC+CA/AA
16/20
50/58
rs1004819
C/T
27/45
81/135
CC+CT/TT
22/14
65/43
rs11209032
G/A
34/38
102/114
GG+GA/AA
28/8
74/34
rs1495965
A/G
33/39
97/119
AA+AG/GG
27/9
73/35
rs6677188
A/T
12/60
41/175
AA+AT/TT
12/24
40/68
*
**
P < 0.05, P < 0.01; P’, after Bonferroni correction.
20
0.81 (0.44,1.49)
0.93 (0.43,1.98)
0.50
0.85
1.00 (0.58,1.72)
1.04 (0.48,2.25)
1.00
0.92
1.00 (0.59,1.68)
1.61 (0.66,3.89)
1.00
0.29
1.04 (0.61,1.76)
1.44 (0.61,3.38)
0.89
0.40
0.83 (0.38,1.80)
0.85 (0.38,1.88)
0.63
0.69