Introduction
Materials and methods
Study population
Patients
Parameter |
n (%) | |||
---|---|---|---|---|
Without GO (n = 28) | CAS + orbitopathy index | 0 | 28 (16.28) | |
With GO (n = 144) | CAS | Non-active (n = 73) | 0 | 10 (5.81) |
1 | 10 (5.81) | |||
2 | 21 (12.21) | |||
3 | 32 (18.60) | |||
Active (n = 71) | 4 | 32 (18.60) | ||
5 | 21 (12.21) | |||
6 | 14 (8.15) | |||
7 | 4 (2.33) | |||
Orbitopathy index | Non-severe (n = 64) | Mild | 29 (16.86) | |
Moderate | 35 (20.35) | |||
Severe | 80 (46.50) | |||
Gender | Female/male | 134 (77.90)/38 (22.10) | ||
Familial autoimmune thyroid history | Yes/no | 138 (80.23)/34 (19.77) | ||
Smoking status | Non-smokers (n = 65) | Never | 65 (37.79) | |
Smokers (n = 107) | In past | 38 (22.09) | ||
≤10 | 40 (23.26) | |||
10–20 | 25 (14.53) | |||
≥20 | 4 (2.33) | |||
Response to anti-thyroid treatment | Yes | 96 (55.82) | ||
No (n = 76) | Thyroidectomy | 16 (9.30) | ||
131I therapy | 60 (34.88) | |||
Age | Mean ± SD | 49 ± 12.73 | ||
Median | 48 | |||
Range | 23–82 |
Assessment of ocular changes
Control group
Ethical approvals
Genotyping of polymorphisms
Statistical analyses
Results
GD patients n (%) | Control group n (%) |
p
global
#
|
χ
2
|
p
| Odds ratio | 95 % confidence interval | |
---|---|---|---|---|---|---|---|
CTLA-4g.*642AT(8_33) | |||||||
Genotype
a
| |||||||
[AT<16]/[AT<16] | 31 (18.0) | 99 (25.4) | 0.08^ |
Referent
| |||
[AT<16]/[AT16–21] | 52 (30.2) | 104 (26.7) | 3.10 | 0.08 | 1.60 | 0.95–2.69 | |
[AT<16]/[AT>21] | 22 (12.8) | 64 (16.5) | 0.08 | 0.77 | 1.10 | 0.58–2.06 | |
[AT16–21]/[AT16–21] | 35 (20.3) | 50 (12.9) |
7.26
|
0.007
|
2.24
|
1.24–4.04
| |
[AT16–21]/[AT>21] | 30 (17.4) | 54 (13.9) | 3.53 | 0.06 | 1.77 | 0.97–3.24 | |
[AT>21]/[AT>21] | 2 (1.2) | 18 (4.6) | 1.21* | 0.27* | 0.35 | 0.08–1.62 | |
Allele
b
| |||||||
[AT<16] | 136 (39.5) | 366 (47.0) |
0.006^ |
Referent
| |||
[AT16–21] | 152 (44.2) | 258 (33.2) |
10.41
|
0.001
|
1.59
|
1.20–2.10
| |
[AT>21] | 56 (16.3) | 154 (19.8) | 0.01 | 1.00 | 0.98 | 0.68–1.41 | |
Dominant model
| |||||||
[AT<16]/[AT16–21] + [AT16–21]/[AT16–21] + [AT16–21]/[AT>21] vs. others | 117 (68.0) | 208 (53.5) |
10.36
|
0.001
|
1.85
|
1.27–2.70
| |
55 (32.0) | 181 (46.5) |
0.54
|
0.37–0.79
| ||||
CT60 (CTLA-4g.*6230G>A, rs3087243) | |||||||
Genotype
c
| |||||||
[GG] | 74 (43.0) | 133 (34.3) | 0.08^ |
Referent
| |||
[GA] | 80 (46.5) | 187 (48.2) | 1.78 | 0.18 | 0.77 | 0.52–1.13 | |
[AA] | 18 (10.5) | 68 (17.5) |
6.19
|
0.01
|
0.48
|
0.26–0.86
| |
Allele
| |||||||
[G] | 228 (66.3) | 453 (58.4) |
6.09
|
0.01
|
1.41
|
1.08–1.84
| |
[A] | 116 (33.7) | 323 (41.6) |
0.72
|
0.55–0.93
| |||
Dominant model
| |||||||
[GG] + [GA] vs. [AA] | 154 (89.7) | 320 (82.5) |
4.57
|
0.03
|
1.82
|
1.05–3.16
| |
18 (10.3) | 68 (17.5) |
0.55
|
0.32–0.96
| ||||
Recessive model
| |||||||
[AA] + [GA] vs. [GG] | 98 (57.0) | 255 (65.7) |
3.91
|
0.05
|
0.69
|
0.48–1.00
| |
74 (43.0) | 134 (34.4) |
1.45
|
1.00–2.09
| ||||
ICOSc.1554+4GT(8_15)
| |||||||
Genotype
d
| |||||||
(s)/(s) | 1 (0.6) | 4 (1.0) | ns^ | 0.00* | 1.00* | 0.58 | 0.06–5.29 |
(s)/(m) | 5 (2.9) | 35 (9.0) |
4.46*
|
0.03*
|
0.33
|
0.13–0.88
| |
(s)/(l) | 7 (4.1) | 17 (4.4) | 0.009 | 1.00 | 0.96 | 0.38–2.41 | |
(m)/(m) | 71 (41.3) | 166 (42.9) |
Referent
| ||||
(m)/(l) | 77 (44.8) | 137 (35.4) | 1.77 | 0.18 | 1.31 | 0.88–1.94 | |
(l)/(l) | 11 (6.4) | 28 (7.2) | 0.06 | 0.81 | 1.10 | 0.52–2.32 | |
Allele
e
| |||||||
(s) | 14 (4.1) | 60 (7.8) | ns^ |
4.58
|
0.03
|
0.52
|
0.29–0.96
|
(m) | 224 (65.1) | 504 (65.1) |
Referent
| ||||
(l) | 106 (30.8) | 210 (27.1) | 0.74 | 0.39 | 0.88 | 0.67–1.17 | |
Dominant model
| |||||||
(m)/(m) + (m)/(l) vs. others | 153 (89.0) | 338 (87.3) | 0.29 | 0.59 | 0.86 | 0.49–1.50 | |
19 (11.0) | 49 (12.7) | 1.17 | 0.67–2.05 |
CD28/CTLA-4/ICOS gene polymorphisms and GD risk
CD28/CTLA-4/ICOS gene polymorphisms and gender
GD risk factors—multivariate associations
CD28/CTLA-4/ICOS gene polymorphisms and clinical data in GD
Familial autoimmune thyroid history
Familial autoimmune thyroid history |
χ
2
|
p-value | Odds ratio | 95 % confidence interval | ||
---|---|---|---|---|---|---|
Without (n = 34) n (%) | With (n = 138) n (%) | |||||
CTLA-4 g.319C>T (rs5742909) | ||||||
Genotype
a
| ||||||
[CC] | 16 (47.1) | 112 (81.2) |
Referent
| |||
[CT] | 16 (47.1) | 24 (17.4) | 14.95 |
0.0001
|
0.21
|
0.09–0.49
|
[TT] | 2 (5.9) | 2 (1.4) | 2.00* | 0.16* | 0.14 | 0.02–1.09 |
Allele
| ||||||
[C] | 48 (70.6) | 248 (89.9) |
16.87
|
4.07 × 10
−5
|
3.69
|
1.92–7.08
|
[T] | 20 (29.4) | 28 (10.1) |
0.27
|
0.14–0.52
| ||
Dominant model
| ||||||
[CC] + [CT] vs. [TT] | 32 (94.1) | 136 (98.6) | 0.81* | 0.37* | 4.25 | 0.58–31.32 |
2 (5.9) | 2 (1.4) | 0.24 | 0.03–1.73 | |||
Recessive model
| ||||||
[TT] + [CT] vs. [CC] | 18 (52.9) | 26 (18.8) |
16.66
|
4.5 × 10
−5
|
0.21
|
0.09–0.46
|
16 (47.1) | 112 (81.2) |
4.85
|
2.18–10.76
| |||
CTLA-4c.49A>G (rs231775) | ||||||
Genotype
b
| ||||||
[AA] | 12 (35.3) | 39 (28.3) |
Referent
| |||
[AG] | 19 (55.9) | 70 (50.7) | 0.09 | 0.76 | 0.88 | 0.39–2.01 |
[GG] | 3 (8.8) | 29 (21.0) | 1.79* | 0.18* | 2.97 | 0.77–11.51 |
Allele
| ||||||
[A] | 43 (63.2) | 148 (53.6) | 2.04 | 0.15 | 0.67 | 0.39–1.16 |
[G] | 25 (36.8) | 128 (46.4) | 1.49 | 0.86–2.57 | ||
Dominant model
| ||||||
[AA] + [AG] vs. [GG] | 31 (91.2) | 109 (79.0) |
3.85*
|
0.05*
|
0.27
|
0.08–0.94
|
3 (8.8) | 29 (21.0) |
3.70
|
1.07–12.78
| |||
Recessive model
| ||||||
[GG] + [AG] vs. [AA] | 22 (64.7) | 99 (71.7) | 0.65 | 0.42 | 1.38 | 0.63–3.07 |
12 (35.3) | 39 (28.3) | 0.72 | 0.33–1.60 | |||
CTLA-4 g.*642AT(8_33) | ||||||
Genotype
c
| ||||||
[AT<16]/[AT<16] | 6 (17.6) | 25 (18.1) |
Referent
| |||
[AT<16]/[AT16–21] | 10 (29.4) | 42 (30.4) | 0.00 | 1.00 | 1.01 | 0.33–3.11 |
[AT<16]/[AT>21] | 6 (17.6) | 16 (11.6) | 0.46 | 0.50 | 0.64 | 0.18–2.33 |
[AT16–21]/[AT16–21] | 6 (17.6) | 29 (21.0) | 0.05 | 0.82 | 1.16 | 0.33–4.06 |
[AT16–21]/[AT>21] | 6 (17.6) | 24 (17.4) | 0.004 | 1.00 | 0.96 | 0.27–3.39 |
[AT>21]/[AT>21] | 0 (0.0) | 2 (1.4) |
4.27*
|
0.04*
|
–
|
–
|
Allele
d
| ||||||
[AT<16] | 28 (41.2) | 108 (39.1) |
Referent
| |||
[AT16–21] | 28 (41.2) | 124 (44.9) | 0.22 | 0.64 | 1.15 | 0.64–2.06 |
[AT>21] | 12 (17.6) | 44 (15.9) | 0.02 | 1.00 | 0.95 | 0.44–2.04 |
Dominant model
| ||||||
[AT<16]/[AT16–21] + [AT16–21]/[AT16–21] + [AT<16]/[AT>21] vs. others | 34 (100.0) | 136 (98.6) | 0.04* | 0.85* | – | – |
0 (0.0) | 2 (1.4) | – | – | |||
ICOS c.1554_4GT(8_15) | ||||||
Genotype
e
| ||||||
(s)/(s) | 0 (0.0) | 1 (0.7) | 0.39* | 0.53* | – | – |
(s)/(m) | 0 (0.0) | 5 (3.6) | 0.47* | 0.49* | – | – |
(s)/(l) | 3 (8.8) | 4 (2.9) | 0.41* | 0.52* | 0.42 | 0.09–2.07 |
(m)/(m) | 17 (50.0) | 54 (39.1) |
Referent
| |||
(m)/(l) | 10 (29.4) | 67 (48.6) | 2.97 | 0.08 | 2.11 | 0.89–4.98 |
(l)/(l) | 4 (11.8) | 7 (5.1) | 0.26* | 0.61* | 0.55 | 0.14–2.11 |
Allele
f
| ||||||
(s) | 3 (4.4) | 11 (4.0) | 0.03* | 0.85* | 0.90 | 0.24–3.35 |
(m) | 44 (647.) | 180 (65.2) |
Referent
| |||
(l) | 21 (30.9) | 85 (30.8) | 0.001 | 1.00 | 0.99 | 0.55–1.77 |
Dominant model
| ||||||
(s)/(m) + (m)/(m) + (m)/(l) vs. others | 27 (79.4) | 126 (91.3) |
3.92
|
0.05
|
2.72
|
0.98–7.55
|
7 (20.6) | 12 (8.7) |
0.37
|
0.13–1.02
| |||
CTLA-4g.319C>T (rs5742909) | Whole genotype |
a
|
χ
2 = 16.89, df = 2, p = 0.0002
| |||
CTLA-4c.49A>G (rs231775) | Whole genotype |
b
|
χ
2 = 2.78, df = 2, p = 0.25 | |||
CTLA-4g.*642AT(8_33) | Whole genotype |
c
|
χ
2 = 1.44, df = 5, p = 0.92 | |||
Whole allele |
d
|
χ
2 = 0.33, df = 2, p = 0.85 | ||||
ICOSc.1554+4GT(8_15) | Whole genotype |
e
|
χ
2 = 8.75, df = 5, p = 0.12 | |||
Whole allele |
f
|
χ
2 = 0.026678, df = 2, p = 0.986749 |
Response to medical treatment
Anti-thyroid treatment |
χ
2
|
p-value | Odds ratio | 95 % confidence interval | ||
---|---|---|---|---|---|---|
Response n (%) | No response n (%) | |||||
CTLA-4g.*642AT(8_33) | ||||||
Genotype
c
| ||||||
[AT<16]/[AT<16] | 22 (22.9) | 9 (11.8) |
Referent
| |||
[AT<16]/[AT16–21] | 28 (29.2) | 24 (31.6) | 2.38 | 0.12 | 2.10 | 0.81–5.41 |
[AT<16]/[AT>21] | 13 (13.5) | 9 (11.8) | 0.81 | 0.37 | 1.69 | 0.54–5.35 |
[AT16–21]/[AT16–21] | 20 (20.8) | 15 (19.7) | 1.36 | 0.24 | 1.83 | 0.66–5.11 |
[AT16–21]/[AT>21] | 13 (13.5) | 17 (22.4) |
4.76
|
0.03
|
3.20
|
1.11–9.22
|
[AT>21]/[AT>21] | 0 (0.0) | 2 (2.6) | 1.66* | 0.20* | – | – |
Allele
d
| ||||||
[AT<16] | 85 (44.3) | 51 (33.6) |
Referent
| |||
[AT16–21] | 81 (42.2) | 71 (46.7) | 2.49 | 0.11 | 1.46 | 0.91–2.34 |
[AT>21] | 26 (13.5) | 30 (19.7) |
4.20
|
0.04
|
1.92
|
1.03–3.61
|
Dominant model
| ||||||
[AT<16]/[AT16–21] + [AT16–21]/[AT16–21] + [AT<16]/[AT>21] vs. others | 61 (63.5) | 56 (73.7) | 2.01 | 0.16 | 1.61 | 0.83–3.10 |
35 (36.5) | 20 (26.3) | 0.62 | 0.32–1.20 | |||
CT60(CTLA-4)(g.*6230G > A, rs3087243) | ||||||
Genotype
e
| ||||||
[GG] | 33 (34.4) | 41 (53.9) |
Referent
| |||
[GA] | 48 (50.0) | 32 (42.1) | 3.66 | 0.06 | 0.54 | 0.28–1.02 |
[AA] | 15 (15.6) | 3 (3.9) |
7.22*
|
0.007*
|
0.16
|
0.04–0.60
|
Allele
| ||||||
[G] | 114 (59.4) | 114 (75.0) |
9.27
|
0.002
|
2.05
|
1.29–3.27
|
[A] | 78 (40.6) | 38 (25.0) |
0.49
|
0.31–0.78
| ||
Dominant model
| ||||||
[GG] + [GA] vs. [AA] | 81 (84.4) | 73 (96.1) |
4.99*
|
0.03*
|
4.51
|
1.25–16.20
|
15 (15.6) | 3 (3.9) |
0.22
|
0.06–0.80
| |||
Recessive model
| ||||||
[AA] + [GA] vs. [GG] | 63 (63.6) | 35 (46.1) |
6.63
|
0.01
|
0.45
|
0.24–0.83
|
33 (34.4) | 41 (53.9) |
2.24
|
1.21–4.15
| |||
Jo31 (CTLA-4)(g.*10223G>T, rs11571302) | ||||||
Genotype
f
| ||||||
[GG] | 28 (29.2) | 35 (46.1) |
Referent
| |||
[GT] | 47 (49.0) | 33 (43.4) | 2.89 | 0.09 | 0.56 | 0.29–1.10 |
[TT] | 21 (21.9) | 8 (10.5) |
6.24
|
0.01
|
0.30
|
0.12–0.79
|
Allele
| ||||||
[G] | 103 (53.6) | 103 (67.8) |
7.04
|
0.008
|
1.82
|
1.17–2.83
|
[T] | 89 (46.4) | 49 (32.2) |
0.55
|
0.35–0.86
| ||
Dominant model
| ||||||
[GG] + [GT] vs. [TT] | 75 (78.1) | 68 (89.5) |
3.90
|
0.05
|
2.38
|
0.99–3.73
|
21 (21.9) | 8 (10.5) |
0.42
|
0.17–1.01
| |||
Recessive model
| ||||||
[TT] + [GT] vs. [GG] |
68 (70.8)
|
41 (53.9)
|
5.21
|
0.02
|
0.48
|
0.26–0.91
|
28 (29.2)
|
35 (46.1)
|
2.07
|
1.10–3.89
| |||
CTLA-4g.*642AT(8_33) | Whole genotype |
c
|
χ
2 = 7.52, df = 5, p = 0.19 | |||
Whole allele |
d
|
χ
2 = 4.86, df = 2, p = 0.09 | ||||
CT60 (CTLA-4g.*6230G>A, rs3087243) | Whole genotype |
e
|
χ
2 = 9.87, df = 2, p = 0.007
| |||
Jo31 (CTLA-4g.*10223G>T, rs11571302) | Whole genotype |
f
|
χ
2 = 6.82, df = 2, p = 0.03
|
Response to medical treatment—multivariate associations
CD28/CTLA-4/ICOS gene polymorphisms and GO
The course of GO—univariate associations
Control group I n (%) | GD patients without GO II n (%) | GD patients with GO III n (%) |
p
global
#
|
χ
2
|
p
| Odds ratio | 95 % confidence interval | ||
---|---|---|---|---|---|---|---|---|---|
CTLA-4g.319C>T (rs5742909) | |||||||||
Genotype
| |||||||||
[CC] | 309 (80.3) | 23 (82.1) | 105 (72.9) |
Referent
| |||||
[CT] | 74 (19.2) | 4 (14.3) | 36 (25.0) | I:II | 0.89 | 0.35 | 0.65 | 0.26–1.60 | |
I:III | 2.40 | 0.12 | 1.43 | 0.91–2.23 | |||||
II:III | 0.91* | 0.34* | 1.97 | 0.64–6.09 | |||||
[TT] | 2 (0.5) | 1 (3.6) | 3 (2.1) | I:II | 0.60* | 0.44 | 8.13 | 0.71–93.74 | |
I:III | 1.55* | 0.21* | 4.41 | 0.73–26.78 | |||||
II:III | 0.09* | 0.76* | 0.66 | 0.07–6.61 | |||||
Allele
| |||||||||
[C] | 692 (89.9) | 50 (89.3) | 246 (85.4) | I:II | 2.28 | 0.13 | 0.56 | 0.27–1.20 | |
I:III |
4.13
|
0.04
|
0.66
|
0.44–0.99
| |||||
II:III | 0.58 | 0.44 | 0.70 | 0.28–1.74 | |||||
[T] | 78 (10.1) | 6 (10.7) | 42 (14.6) | I:II | 2.28 | 0.13 | 1.77 | 0.84–3.77 | |
I:III |
4.13
|
0.04
|
1.51
|
1.01–2.27
| |||||
II:III | 0.58 | 0.44 | 1.42 | 0.57–3.53 | |||||
Dominant model
| |||||||||
[CC] + [CT] vs. [TT] | 383 (99.5) | 27 (96.4) | 141 (97.9) | I:II | 0.47* | 0.49* | 0.14 | 0.01–1.61 | |
I:III | 1.32* | 0.25* | 0.25 | 0.04–1.48 | |||||
II:III | 0.04* | 0.84* | 1.74 | 0.17–17.37 | |||||
2 (0.5) | 1 (3.6) | 3 (2.1) | I:II | 0.47* | 0.49* | 7.09 | 0.62–80.72 | ||
I:III | 1.32* | 0.25* | 4.07 | 0.67–24.64 | |||||
II:III | 0.04* | 0.84* | 0.57 | 0.06–5.73 | |||||
Recessive model
| |||||||||
[TT] + [CT] vs. [CC] | 76 (19.7) | 5 (17.9) | 39 (24.8) | I:II | 0.00* | 1.00* | 0.88 | 0.33–2.40 | |
I:III | 3.32* | 0.07* | 0.66 | 0.42–1.03 | |||||
II:III | 0.62* | 0.43* | 1.71 | 0.61–4.81 | |||||
309 (80.3) | 23 (82.1) | 105 (72.9) | I:II | 0.00* | 1.00* | 1.13 | 0.42–3.07 | ||
I:III | 3.32* | 0.07* | 1.51 | 0.97–2.36 | |||||
II:III | 0.62* | 0.43* | 0.59 | 0.21–1.65 | |||||
CTLA-4g.*642AT(8_33) | |||||||||
Genotype
c
| |||||||||
[AT<16]/[AT<16] | 99 (25.4) | 4 (14.3) | 27 (18.8) |
Referent
| |||||
[AT<16]/[AT16–21] | 104 (26.7) | 12 (42.9) | 40 (27.8) | I:II | 2.48* | 0.12* | 2.86 | 0.89–9.15 | |
I:III | 1.45 | 0.23 | 1.41 | 0.81–2.47 | |||||
II:III | 0.72* | 0.40* | 0.49 | 0.14–1.69 | |||||
[AT<16]/[AT>21] | 64 (16.5) | 2 (7.1) | 20 (13.9) | I:II | 0.02* | 1.00* | 0.77 | 0.14–4.35 | |
I:III | 0.16 | 0.69 | 1.15 | 0.59–2.21 | |||||
II:III | 0.00* | 1.00* | 1.48 | 0.25–8.90 | |||||
[AT16–21]/[AT16–21] | 50 (12.9) | 2 (7.1) | 33 (22.9) | I:II | 0.19* | 0.67* | 0.99 | 0.18–5.59 | |
I:III |
8.22
|
0.004
|
2.42
|
1.31–4.46
| |||||
II:III | 0.34* | 0.56* | 2.44 | 0.42–14.38 | |||||
[AT16–21]/[AT>21] | 54 (13.9) | 6 (21.4) | 24 (16.7) | I:II | 1.52* | 0.22* | 2.75 | 0.74–10.17 | |
I:III | 2.24 | 0.13 | 1.63 | 0.86–3.10 | |||||
II:III | 0.16* | 0.69* | 0.59 | 0.15–2.35 | |||||
[AT>21]/[AT>21] | 18 (4.6) | 2 (7.1) | 0 (0.0) | I:II | 0.35* | 0.55* | 2.75 | 0.47–16.15 | |
I:III | 3.45* | 0.06* | – | – | |||||
II:III |
4.62*
|
0.03*
| – | – | |||||
Allele
d
| |||||||||
[AT<16] | 366 (47.0) | 22 (39.3) | 114 (39.6) | ns |
Referent
| ||||
[AT16–21] | 258 (33.2) | 22 (39.3) | 130 (45.1) | I:II | 1.26 | 0.26 | 1.42 | 0.77–2.62 | |
I:III |
10.10
|
0.001
|
1.62
|
1.20–2.18
| |||||
II:III | 0.16 | 0.69 | 1.14 | 0.60–2.17 | |||||
[AT>21] | 154 (19.8) | 12 (21.4) | 44 (15.3) | I:II | 0.49 | 0.48 | 1.30 | 0.63–2.69 | |
I:III | 0.18 | 0.67 | 0.92 | 0.62–1.36 | |||||
II:III | 0.75 | 0.39 | 0.71 | 0.32–1.55 | |||||
Dominant model
| |||||||||
[AT<16]/[AT16–21] + [AT<16]/[AT>21] + [AT16–21]/[AT16–21] vs. others | 203 (53.6) | 20 (71.4) | 97 (67.4) | I:II | 3.36 | 0.07 | 2.17 | 0.93–5.04 | |
I:III |
8.12
|
0.004
|
1.79
|
1.20–2.68
| |||||
II:III | 0.18 | 0.67 | 0.83 | 0.34–2.01 | |||||
176 (46.4) | 8 (28.6) | 47 (32.6) | I:II | 3.36 | 0.07 | 0.46 | 0.20–1.07 | ||
I:III |
8.12
|
0.004
|
0.56
|
0.37–0.84
| |||||
II:III | 0.18 | 0.67 | 1.21 | 0.50–2.95 | |||||
CT60 (CTLA-4)(g.*6230G>A, rs3087243) | |||||||||
Genotype
e
| |||||||||
[GG] | 133 (34.3) | 9 (32.1) | 65 (45.1) |
Referent
| |||||
[GA] | 187 (48.2) | 17 (60.7) | 63 (43.8) | I:II | 0.48 | 0.49 | 1.34 | 0.58–3.11 | |
I:III | 2.79 | 0.09 | 0.69 | 0.46–1.04 | |||||
II:III | 2.23 | 0.13 | 0.51 | 0.21–1.24 | |||||
[AA] | 68 (17.5) | 2 (7.1) | 16 (11.1) | I:II | 0.56* | 0.46* | 0.43 | 0.09–2.07 | |
I:III |
5.47
|
0.02
|
0.48
|
0.26–0.90
| |||||
II:III | 0.08* | 0.78* | 1.11 | 0.22–5.64 | |||||
Allele
| |||||||||
[G] | 453 (58.4) | 35 (62.5) | 193 (67.0) | I:II | 0.37 | 0.55 | 1.19 | 0.68–2.08 | |
I:III |
6.57
|
0.01
|
1.45
|
1.09–1.93
| |||||
II:III | 0.43 | 0.51 | 1.22 | 0.67–2.21 | |||||
[A] | 323 (41.6) | 21 (37.5) | 95 (33.0) | I:II | 0.37 | 0.55 | 0.84 | 0.48–1.47 | |
I:III |
6.57
|
0.01
|
0.69
|
0.52–0.92
| |||||
II:III | 0.43 | 0.51 | 0.82 | 0.45–1.49 | |||||
Dominant model
| |||||||||
[GG] + [GA] vs. [AA] | 320 (82.5) | 26 (92.9) | 128 (88.9) | I:II | 1.34* | 0.25* | 2.76 | 0.64–11.92 | |
I:III | 3.25 | 0.07 | 1.70 | 0.95–3.04 | |||||
II:III | 0.08* | 0.77* | 0.62 | 0.13–2.84 | |||||
68 (17.5) | 2 (7.1) | 16 (11.1) | I:II | 1.34* | 0.25* | 0.36 | 0.08–1.56 | ||
I:III | 3.25 | 0.07 | 0.59 | 0.33–1.05 | |||||
II:III | 0.08* | 0.77* | 1.63 | 0.35–7.50 | |||||
Recessive model
| |||||||||
[AA] + [GA] vs. [GG] | 255 (65.7) | 19 (67.9) | 79 (54.9) | I:II | 0.06 | 0.80 | 1.11 | 0.49–2.52 | |
I:III |
5.14
|
0.02
|
0.64
|
0.43–0.94
| |||||
II:III | 1.62 | 0.20 | 0.58 | 0.24–1.36 | |||||
134 (34.4) | 9 (32.1) | 65 (45.1) | I:II | 0.06 | 0.80 | 0.90 | 0.40–2.05 | ||
I:III |
5.14
|
0.02
|
1.57
|
1.06–2.31
| |||||
II:III | 1.62 | 0.20 | 1.74 | 0.74–4.10 |