Our study population included data from 304 individuals. To investigate the frequency of selected gene polymorphisms, subjects were divided into two groups. The group of ON patients included 79 subjects: 26 (32.9%) males and 53 (67.1%) females. The control group included 225 subjects: 91 (40.4%) males and 134 (59.6%) females. There was no statistically significant difference between males and females with ON and the control groups (p = 0.236). The mean age was 37 years in the patients with ON and 32 years in the control group. No statistically significant differences were found between the groups by age (p = 0.066). The distribution of subjects by gender and age is shown in Table 1.
Table 1
Demographic characteristics of study subjects.
Characteristic
|
Group
|
p-value
|
Patients with ON
|
Reference group
|
Males, n (%)
|
26 (32.9)
|
91 (40.4)
|
0.236
|
Females, n (%.)
|
53 (67.1)
|
134 (59.6)
|
The median age (IQR)
|
37 (23)
|
32 (17)
|
0.066
|
ON – optic neuritis; IQR – interquartile range; p-value – significance level (statistically significant, when p < 0.05); |
Associations between SIRT1 concentration, optic neuritis, and multiple sclerosis.
Blood serum SIRT1 concentrations were determined in patients with ON (n = 23) and the control group (n = 24). Statistically significant differences were not observed between these groups (IQR: 2.130 ng/ml (1.68) vs. 2.130 ng/ml (0.61), respectively, p = 0.856).
Also, serum SIRT1 levels were compared between ON patients with MS and ON patients without MS subgroups. We also found no statistically significant differences between these two groups (IQR: 3.821 ng/ml (4.35) vs. 2.124 ng/ml (0.61) respectively, p = 0.593).
No statistically significant differences in serum SIRT1 levels were found between ON patients with MS and the control group (IQR: 3.821 ng/ml (4.35) vs. 2.130 ng/ml (0.61), p = 0.695) or between ON patients without MS and the control group (IQR: 2.124 ng/ml (0.61), 2.130 ng/ml (0.61), p = 0.989).
SIRT1 rs3818292, rs3758391, rs7895833 genotypes associations with ON
We determined the frequency of genotypes and alleles of SIRT1 rs3818292, rs3758391, and rs7895833 SNPs compared between ON patients and control groups. The distribution of genotypes and alleles in the control group was in accordance with the Hardy-Weinberg equilibrium (p > 0.001).
There was no statistically significant difference in the frequency of genotypes and alleles of SIRT1 rs3818292 in ON patients and control groups (p = 0.067 and p = 0.383, respectively) (Table 2).
There was a statistically significant difference in C/C and C/T genotypes distribution between patients with ON and control groups. The C/C genotype of SIRT1 rs3758391 was less frequent and the C/T genotype was more frequent in the patients of ON than in the control group (39.2% vs. 56.0%, p = 0.010; 53.2% vs. 36.0%, p = 0.007, respectively) (Table 2).
In addition, a statistically significant difference was found between the distribution of SIRT1 rs7895833 A/A and A/G genotypes. In patients with ON, the A/A genotype was less frequent, and the A/G genotype was more frequent than in the control group (57.0% vs. 73.8%, p = 0.007; 41.8% vs. 20.9%, p = 0.001, respectively) (Table 2).
Table 2
SIRT1 rs3818292, rs3758391, rs7895833 genotypes and alleles frequencies.
Polymorphism
|
Genotype/allele
|
Frequency (%)
|
Control group, n (%)
N = 225
|
HWE p-value
|
Patients with ON, n (%) N = 79
|
p-value
|
rs3818292
|
Genotype
|
A/A
|
192 (85.3)
|
0.003
|
62 (78.5)
|
0.067
|
A/G
|
28 (12.4)
|
17 (21.5)
|
G/G
|
5 (2.2)
|
0 (0)
|
Total
|
225 (100)
|
79 (100)
|
Allele
|
A
|
412 (91.6)
|
|
141 (89.2)
|
0.383
|
G
|
38 (8.4)
|
17 (10.8)
|
rs3758391
|
Genotype
|
C/C
|
126 (56.0)1
|
0.334
|
31 (39.2)1
|
0.024
|
C/T
|
81 (36.0)2
|
42 (53.2)2
|
T/T
|
18 (8.0)
|
6 (7.6)
|
Total
|
225 (100)
|
79 (100)
|
Allele
|
C
|
333 (74.0)
|
|
104 (65.8)
|
0.062
|
T
|
117 (26.0)
|
54 (34.2)
|
rs7895833
|
Genotype
|
A/A
|
166 (73.8)3
|
0.001
|
45 (57.0)3
|
0.001
|
A/G
|
47 (20.9)4
|
33 (41.8)4
|
G/G
|
12 (5.3)
|
1 (1.3)
|
Total
|
225 (100)
|
79 (100)
|
Allele
|
A
|
379 (84.2)
|
|
123 (77.8)
|
0.069
|
G
|
71 (15.8)
|
35 (22.2)
|
ON – optic neuritis; p value - significance level (statistically significant, then p < 0.05); HVE p-value – significance level according to Hardy-Weinberg equilibrium principle (differences are considered significant, when p < 0.001); 1 – p = 0.010; 2 – p = 0.007; 3 – p = 0.007; 4 – p = 0.001; |
Binary logistic regression analysis of SIRT1 rs3818292, rs3758391, and rs7895833 was performed. It was found that SIRT1 rs3758391 C/T genotype was associated with a 2.1-fold increased probability of developing ON compared to C/C genotype (OR = 2.108; 95%. CI 1.226–3.622; p = 0.007). The C/T + T/T genotypes were associated with a 2-fold increased odds of developing ON compared to the C/C genotype (OR = 1.971; 95%. CI 1.168–3.324; p = 0.011) and the C/T genotype was associated with a 2.7-fold increased odds of developing ON compared to the C/C + T/T genotype (OR = 2.717; 95%. CI 1.566–4.712; p = 0.008) (Table 3).
The SIRT1 rs7895833 A/G genotype was associated with a 2.6-fold increased likelihood of developing ON than the A/A genotype (OR = 2.590; 95% CI 1.489–4.506; p = 0.001). The A/G + G/G genotypes were associated with a 2.1-fold increased odds of developing ON compared to the A/A genotype (OR = 2.126; 95%, CI 1.245–3.631; p = 0.006), and the A/G genotype was associated with a 2.7-fold increased odds of developing ON compared to the A/A + G/G genotype (OR = 2.717; 95%, CI 1.566–4.712; p < 0.001) (Table 3).
Table 3
SIRT1 rs3818292, rs3758391, rs7895833 binary logistic regression between ON and control groups.
Polymorphism
|
Model
|
Genotype
|
OR (95% CI)
|
p-value
|
AIC
|
rs3818292
|
Codominant
|
A/A
|
1
|
0.064
1
|
345.990
|
A/G
|
1.880 (0.865–3.664)
|
G/G
|
–
|
Dominant
|
A/A
|
1
|
0.160
|
348.426
|
A/G + G/G
|
1.595 (0.832–3.060)
|
Recessive
|
AA + A/G
|
1
|
1
|
347.296
|
G/G
|
–
|
Overdominant
|
A/A + G/G
|
1
|
0.053
|
346.261
|
A/G
|
1.929 (0.990–3.758)
|
Additive
|
G
|
1.275 (0.718–2.264)
|
0.407
|
349.667
|
rs3758391
|
Codominant
|
C/C
|
1
|
0.007
0.553
|
344.935
|
C/T
|
2.108 (1.226–3.622)
|
T/T
|
1.355 (0.496–3.698)
|
Dominant
|
C/C
|
1
|
0.011
|
343.729
|
C/T + T/T
|
1.971 (1.168–3.324)
|
Recessive
|
C/C + C/T
|
1
|
0.909
|
350.322
|
T/T
|
0.945 (0.361–2.473)
|
Overdominant
|
C/C + T/T
|
1
|
0.008
|
343.274
|
C/T
|
2.018 (1.201–3.391)
|
Additive
|
T
|
1.482 (0.999–2.199)
|
0.051
|
346.545
|
rs7895833
|
Codominant
|
A/A
|
1
|
0.001
0.574
|
338.196
|
A/G
|
2.590 (1.489–4.506)
|
G/G
|
0.574 (0.025–7.691)
|
Dominant
|
A/A
|
1
|
0.006
|
342.826
|
A/G + G/G
|
2.126 (1.245–3.631)
|
Recessive
|
AA + A/G
|
1
|
0.158
|
347.368
|
G/G
|
0.228 (0.029–1.779)
|
Overdominant
|
A/A + G/G
|
1
|
< 0.001
|
337.908
|
A/G
|
2.717 (1.566–4.712)
|
Additive
|
G
|
1.470 (0.950–2.276)
|
0.084
|
347.415
|
p-value – significance level (differences are considered significant when p < 0.05); OR – odds ratio; CI – confidence interval; AIC – Akaike information criterion. |
SIRT1 rs3818292, rs3758391, rs7895833 genotypes associations with ON according to gender and morbidity of MS.
We compared the distribution of genotypes and alleles of SIRT1 rs3818292, rs3758391, and rs7895833 in ON and control groups by sex.
The analysis showed that SIRT1 rs7895833 A/A genotype was less frequent, while A/G genotype was more frequent in women with ON than in the control group (56.6% vs. 74.6%, p = 0.022; 41.5% vs. 20.9%, p = 0.006, respectively. We found no statistically significant differences in the male groups (Table 4).
Table 4
SIRT1 rs3818292, rs3758391, rs7895833 genotypes and alleles frequencies in patients with ON by gender.
Polymorphism
|
Genotype
|
Frequency, n (%)
|
Males
|
p-value
|
Females
|
p-value
|
Control group,
n (%)
N = 91
|
Patients with ON, n (%)
N = 26
|
Control group,
n (%)
N = 134
|
Patients with ON, n (%)
N = 53
|
rs3818292
|
A/A
|
80 (87.9)
|
21 (80.8)
|
0.788
|
112 (83.6)
|
41 (77.4)
|
0.492
|
A/G
|
7 (7.7)
|
5 (19.2)
|
21 (15.7)
|
12 (22.6)
|
G/G
|
4 (4.4)
|
0 (0)
|
1 (0.7)
|
0 (0)
|
Allele
|
A
|
167 (91.8)
|
47 (90.4)
|
0.755
|
245 (91.4)
|
94 (88.7)
|
0.412
|
G
|
15 (8.2)
|
5 (9.6)
|
23 (8.6)
|
12 (11.3)
|
rs3758391
|
Genotype
|
C/C
|
48 (52.7)
|
10 (38.5)
|
0.385
|
78 (58.2)
|
21 (39.6)
|
0.056
|
C/T
|
32 (35.2)
|
13 (50)
|
49 (36.6)
|
29 (54.7)
|
T/T
|
11 (12.1)
|
3 (11.5)
|
7 (5.2)
|
3 (5.7)
|
Allele
|
C
|
128 (70.3)
|
33 (63.5)
|
0.346
|
205 (76.5)
|
71 (67.0)
|
0.594
|
T
|
54 (29.7)
|
19 (36.5)
|
63 (23.5)
|
35 (33.0)
|
rs7895833
|
Genotype
|
A/A
|
66 (72.5)
|
15 (57.7)
|
0.067
|
100 (74.6)1
|
30 (56.6)1
|
0.014
|
A/G
|
19 (20.9)
|
11 (42.3)
|
28 (20.9)2
|
22 (41.5)2
|
G/G
|
6 (6.6)
|
0 (0)
|
6 (4.5)
|
1 (1.9)
|
Allele
|
A
|
151 (83.0)
|
41 (78.8)
|
0.495
|
228 (85.1)
|
82 (77.4)
|
0.074
|
G
|
31 (17.0)
|
11 (21.2)
|
40 (14.9)
|
24 (22.6)
|
ON – optic neuritis; p-value - significance level (differences are considered significant, when p < 0.05); 1 – (A/A vs. A/G + G/G) p = 0.022; 2 – (A/G vs. A/A + G/G) p = 0.006; |
Binary logistic regression analysis of SIRT1 rs3818292, rs3758391, and rs7895833 in patients with ON and control groups by sex was performed. In the male group, we observed that the A/G genotype of SIRT1 rs7895833 was associated with a 2.6-fold increased likelihood of developing ON compared to the A/A genotype (OR = 2.547; 95%. CI 1.005–6.459; p = 0.049) and the A/G genotype was associated with a 2.8-fold increased odds of developing ON in males compared to the A/A and G/G genotypes (OR = 2.779; 95%. CI 1.099–7.028; p = 0.031) (Table 5).
In the female group, we found that the C/T genotype of SIRT1 rs3758391 was associated with a 2.2-fold increased likelihood of developing ON compared with the C/C genotype (OR = 2.198; 95%. CI 1.130–4.277; p = 0.020). The C/T + T/T genotypes were associated with a 2.1-fold increased odds of developing ON compared to the C/C genotype (OR = 2.122; 95%. CI 1.109–4.060; p = 0.023) and the C/T genotype was also associated with a 2.1-fold increased odds of developing ON compared to the C/C and T/T genotypes in females (OR = 2.096; 95%. CI 1.100–3.995; p = 0.025) (Table 6).
The A/G genotype of SIRT1 rs7895833 was associated with a 2.6-fold increased probability of developing ON compared to the A/A genotype (OR = 2.619; 95%. CI 1.312–5.230; p = 0.006). Genotypes A/G + G/G were associated with a 2.2-fold increased odds of developing ON compared to genotype A/A (OR = 2.255; 95%. CI 1.156–4.399; p = 0.017), and genotype A/G was associated with a 2.7-fold increased odds of developing ON in females compared to genotype A/A + G/G (OR = 2.68; 95%. CI (1.352–5.340); p = 0.005) (Table 6).
Table 5
Binary logistic regression for SIRT1 rs3818292, rs3758391, between males of ON and control groups.
Polymorphism
|
Model
|
Genotype
|
OR (95%. CI)
|
p-value
|
AIC
|
rs3818292
|
Codominant
|
A/A
|
1
|
0.115
1
|
123.561
|
A/G
|
2.721 (0.784–9.443)
|
G/G
|
–
|
Dominant
|
A/A
|
1
|
0.354
|
125.135
|
A/G + G/G
|
1.732 (0.542–5.531)
|
Recessive
|
AA + A/G
|
1
|
1
|
123.901
|
G/G
|
–
|
Overdominant
|
A/A + G/G
|
1
|
0.098
|
123.358
|
A/G
|
2.857 (0.824–9.906)
|
Additive
|
G
|
1.134 (0.455–2.825)
|
0.788
|
125.881
|
rs3758391
|
Codominant
|
C/C
|
1
|
0.163
0.715
|
125.976
|
C/T
|
1.950 (0.763–4.982)
|
T/T
|
1.309 (0.308–5.564)
|
Dominant
|
C/C
|
1
|
0.202
|
124.228
|
C/T + T/T
|
1.786 (0.733–4.353)
|
Recessive
|
C/C + C/T
|
1
|
0.939
|
125.945
|
T/T
|
0.949 (0.244–3.689)
|
Overdominant
|
C/C + T/T
|
1
|
0.173
|
124.106
|
C/T
|
1.844 (0.764–4.450)
|
Additive
|
T
|
1.326 (0.714–2.460)
|
0.371
|
125.162
|
rs7895833
|
Codominant
|
A/A
|
1
|
0.049
1
|
121.054
|
A/G
|
2.547 (1.005–6.459)
|
G/G
|
–
|
Dominant
|
A/A
|
1
|
0.152
|
123.941
|
A/G + G/G
|
1.936 (0.784–4.781)
|
Recessive
|
AA + A/G
|
1
|
1
|
122.844
|
G/G
|
–
|
Overdominant
|
A/A + G/G
|
1
|
0.031
|
121.416
|
A/G
|
2.779 (1.099–7.028)
|
Additive
|
G
|
1.267 (0.614–2.611)
|
0.522
|
125.551
|
p-value - significance level (differences are considered significant when p < 0,05); OR – odds ratio; CI – confidence interval; AIC – Akaike information criterion. |
Table 6
Binary logistic regression for SIRT1 rs3818292, rs3758391, between females of ON and control groups.
Polymorphism
|
Model
|
Genotype
|
OR (95%. CI)
|
p-value
|
AIC
|
rs3818292
|
Codominant
|
A/A
|
1
|
0.272
1
|
225.119
|
A/G
|
1.561 (0.705–3.455)
|
G/G
|
–
|
Dominant
|
A/A
|
1
|
0.322
|
224.006
|
A/G + G/G
|
1.490 (0.677–3.280)
|
Recessive
|
AA + A/G
|
1
|
1
|
224.294
|
G/G
|
–
|
Overdominant
|
A/A + G/G
|
1
|
0.262
|
223.741
|
A/G
|
1.575 (0.712–3.485)
|
Additive
|
G
|
1.379 (0.648–2.937)
|
0.405
|
224.285
|
rs3758391
|
Codominant
|
C/C
|
1
|
0.020
0.526
|
221.480
|
C/T
|
2.198 (1.130–4.277)
|
T/T
|
1.592 (0.379–6.690)
|
Dominant
|
C/C
|
1
|
0.023
|
219.682
|
C/T + T/T
|
2.122 (1.109–4.060)
|
Recessive
|
C/C + C/T
|
1
|
0.905
|
224.948
|
T/T
|
1.089 (0.271–4.377)
|
Overdominant
|
C/C + T/T
|
1
|
0.025
|
219.862
|
C/T
|
2.096 (1.100–3.995)
|
Additive
|
T
|
1.684 (0.995–2.849)
|
0.052
|
221.181
|
rs7895833
|
Codominant
|
A/A
|
1
|
0.006
0.593
|
218.788
|
A/G
|
2.619 (1.312–5.230)
|
G/G
|
0.556 (0.064–4.798)
|
Dominant
|
A/A
|
1
|
0.017
|
219.336
|
A/G + G/G
|
2.255 (1.156–4.399)
|
Recessive
|
AA + A/G
|
1
|
0.415
|
224.157
|
G/G
|
0.410 (0.048–3.492)
|
Overdominant
|
A/A + G/G
|
1
|
0.005
|
217.111
|
A/G
|
2.687 (1.352–5.340)
|
Additive
|
G
|
1.627 (0.933–2.837)
|
0.086
|
222.068
|
p-value - significance level (differences are considered significant when p < 0,05); OR – odds ratio; CI – confidence interval; AIC – Akaike information criterion; |
We studied the genotypes and allele distribution of SIRT1 rs3818292, rs3758391, and rs7895833 in ON patients and control groups with and without MS.
We found that the SIRT1 rs3758391 C/C was less frequent, and the C/T genotype was more frequent in ON patients with MS than in the control group (30%. vs. 60%, p = 0.007; 56.7%. vs. 36%, p = 0.029, respectively). The T allele was more frequent in ON patients with MS compared to the control group (41.7% vs. 26.0%, p = 0.011) (Table 7).
In addition, statistically significant differences were found in the distribution of SIRT1 rs895833 genotypes A/A, A/G, and G/G in ON patients with MS and the control group (p = 0.001). The A/A genotype was less frequent, and the A/G genotype was more frequent in ON patients with MS than in the control group (43.4% vs. 73.8%, p = 0001; 53.3% vs. 20.9%, p < 0.001, respectively). The G allele was also more frequent in ON patients with MS than in the control group (30.0% vs. 15.8%, p = 0.006) (Table 7).
Table 7
SIRT1 rs3818292, rs3758391, rs7895833 genotypes and alleles frequencies for ON patients with and without MS and control group.
Polymorphism
|
Genotype
|
Frequencies, n (proc.)
|
Control group, n (%)
N = 225
|
ON patients with MS, n (%)
N = 30
|
p-value
|
ON patients with MS, n (%)
N = 43
|
p-value
|
rs3818292
|
Genotype
|
A/A
|
192 (85.3)
|
23 (76.7)
|
0.243
|
34 (79.1)
|
0.250
|
A/G
|
28 (12.4)
|
7 (23.3)
|
9 (20.9)
|
G/G
|
5 (2.2)
|
0 (0)
|
0 (0)
|
Allele
|
A
|
412 (91.6)
|
53 (88.3)
|
0.408
|
77 (89.5)
|
0.544
|
G
|
38 (8.4)
|
7 (11.7)
|
9 (10.5)
|
rs3758391
|
Genotype
|
C/C
|
126 (56.0)1
|
9 (30.0)1
|
0.023
|
20 (46.5)
|
0.270
|
C/T
|
81 (36.0)2
|
17 (56.7)2
|
21 (48.8)
|
T/T
|
18 (8.0)
|
4 (13.3)
|
2 (4.7)
|
Allele
|
A
|
333 (74.0)
|
35 (58.3)
|
0.011
|
61 (70.9)
|
0.554
|
G
|
117 (26.0)
|
25 (41.7)
|
25 (29.1)
|
rs7895833
|
Genotype
|
A/A
|
166 (73.8)3
|
13 (43.4)3
|
0.001
|
29 (67.4)
|
0.107
|
A/G
|
47 (20.9)4
|
16 (53.3)4
|
14 (32.6)
|
G/G
|
12 (5.3)
|
1 (3.3)
|
0 (0)
|
Allele
|
A
|
379 (84,2)
|
42 (70,0)
|
0.006
|
72 (83.7)
|
0.907
|
G
|
71 (15,8)
|
18 (30,0)
|
14 (16.3)
|
ON – optical neuritis; MS – multiple sclerosis; p-value - significance level (differences are considered significant, when p < 0,05); 1 – p = 0,007; 2 – p = 0,029; 3 – p = 0,001; 4 – p < 0,001 |
We performed binary logistic regression analysis to evaluate the influence of SIRT1 rs3818292, rs3758391, and rs7895833 on the development of ON in patients with and without MS.
We found that the C/T and T/T genotypes SIRT1 rs3758391 together were associated with a 3-fold increased odds of ON patients with MS (OR = 2.970; 95%. CI 1.303–6.770; p = 0.010), and the C/T genotype was associated with a 2.2-fold increased odds of ON patients with MS while compared with C/C and T/T genotypes (OR = 2.235; 95% CI 1.075–5.030; p = 0.032). The T allele was associated with a 1.2-fold increased odds of ON with MS (OR = 1.199; 95% CI 1.143–3.450; p = 0.015) (Table 8).
The A/G genotype of SIRT1 rs7895833 was associated with a 4.4-fold increased odds of developing ON with MS compared with the A/A genotype (OR = 4.347; 95%. CI 1.953–9.677; p < 0.001), A/G + G/G genotypes were associated with 3.7-fold increased odds of ON in patients with MS compared to A/A genotype (OR = 3.679; 95% CI 1.685–8.033; p = 0.001) and A/G genotype was associated with 4.3-fold increased odds of ON in patients with MS compared to A/A and G/G genotype (OR = 4.328; 95% CI 1.972–9.499; p < 0.001). At least one G allele was associated with a 2.1-fold increased odds of ON with MS (OR = 2.058; 95% CI 1.162–3.645; p = 0.013) (Table 8).
Table 8
Binary logistic regression for SIRT1 rs3818292, rs3758391, between ON patients with MS and the control group.
Polymorphism
|
Model
|
Genotype
|
OR (95% CI)
|
p-value
|
AIC
|
rs3818292
|
Codominant
|
A/A
|
1
|
0.123
1
|
185292
|
A/G
|
2.087 (0.820 − 5.312)
|
G/G
|
–
|
Dominant
|
A/A
|
1
|
0.225
|
185.362
|
A/G + G/G
|
1.771 (0.703–4.457)
|
Recessive
|
AA + A/G
|
1
|
1
|
185.462
|
G/G
|
–
|
Overdominant
|
A/A + G/G
|
1
|
0.110
|
184.409
|
A/G
|
2.141 (0.841–5449)
|
Additive
|
G
|
1.364 (0617–3.013)
|
0.443
|
186.178
|
rs3758391
|
Codominant
|
C/C
|
1
|
0.082
0.926
|
181.417
|
C/T
|
0.321 (0.090–1.153)
|
T/T
|
0.994 (0.284–3.145)
|
Dominant
|
C/C
|
1
|
0.010
|
179.425
|
C/T + T/T
|
2.970 (1,303–6.770)
|
Recessive
|
C/C + C/T
|
1
|
0.334
|
185.879
|
T/T
|
1.769 (0.556–5.630)
|
Overdominant
|
C/C + T/T
|
1
|
0.032
|
182.090
|
C/T
|
2.235 (1.075–5.030)
|
Additive
|
T
|
1.199 (1.143–3450)
|
0.015
|
178.919
|
rs7895833
|
Codominant
|
A/A
|
1
|
< 0.001
0.954
|
175.665
|
A/G
|
4.347 (1.953–9.677)
|
G/G
|
1.064 (0.128–8.836)
|
Dominant
|
A/A
|
1
|
0.001
|
176.008
|
A/G + G/G
|
3.679 (1.685–8.033)
|
Recessive
|
AA + A/G
|
1
|
0.643
|
186.483
|
G/G
|
0.612 (0.077–4.882)
|
Overdominant
|
A/A + G/G
|
1
|
< 0.001
|
173.668
|
A/G
|
4.328 (1.972–9.499)
|
Additive
|
G
|
2.058 (1.162–3.645)
|
0.013
|
181.025
|
p-value - significance level (differences are considered significant when p < 0,05); OR – odds ratio; CI – confidence interval; AIC – Akaike information criterion; |
Table 9
Binary logistic regression for SIRT1 rs3818292, rs3758391, between ON patients without MS and the control group.
Polymorphism
|
Model
|
Genotype
|
OR (95% CI)
|
p-value
|
AIC
|
rs3818292
|
Codominant
|
A/A
|
1
|
0.162
1
|
236.466
|
A/G
|
1.815 (0.788–4.183)
|
G/G
|
–
|
Dominant
|
A/A
|
1
|
0.303
|
237.056
|
A/G + G/G
|
1.540 (0.677–3.505)
|
Recessive
|
AA + A/G
|
1
|
1
|
236.294
|
G/G
|
–
|
Overdominant
|
A/A + G/G
|
1
|
0.144
|
236.077
|
A/G
|
1.862 (0.808–4.291)
|
Additive
|
G
|
1.230 (0.602–2.516)
|
0.570
|
237.752
|
rs3758391
|
Codominant
|
C/C
|
1
|
0.153
0.649
|
237.368
|
C/T
|
1.633 (0.833–3.201)
|
T/T
|
0.700 (0.151–3.249)
|
Dominant
|
C/C
|
1
|
0.254
|
236.755
|
C/T + T/T
|
1.464 (0.761–2.816)
|
Recessive
|
C/C + C/T
|
1
|
0.450
|
237.405
|
T/T
|
0.561 (0.125–2.511)
|
Overdominant
|
C/C + T/T
|
1
|
0.115
|
235.592
|
C/T
|
1.697 (0.880–3.273)
|
Additive
|
T
|
1.162 (0.701–1.927)
|
0.599
|
237.724
|
rs7895833
|
Codominant
|
A/A
|
1
|
0.144
1
|
233.706
|
A/G
|
1.705 (0.834–3.487)
|
G/G
|
–
|
Dominant
|
A/A
|
1
|
0.394
|
237.351
|
A/G + G/G
|
1.358 (0.672–2.745)
|
Recessive
|
AA + A/G
|
1
|
1
|
233.757
|
G/G
|
–
|
Overdominant
|
A/A + G/G
|
1
|
0.098
|
233.447
|
A/G
|
1.828 (0.895–3.735)
|
Additive
|
G
|
1.033 (0.576–1.853)
|
0.913
|
238.049
|
p-value - significance level (differences are considered significant when p < 0,05); OR – odds ratio; CI – confidence interval; AIC – Akaike information criterion; |
SIRT1 serum levels and SIRT1 rs3818292, rs3758391, rs7895833 associations with ON.
We compared the serum levels of ON patients and the control group according to the SIRT1 SNPs genotypes. Because of the small subject group, we formed two groups: homozygous with the more common allele and heterozygous and homozygous with the less common allele together.
First, serum SIRT1 levels were compared in all subjects. There was no statistically significant difference in SIRT1 serum levels between subjects with the A/A genotype and with the A/G and G/G genotypes for the SIRT1 rs3818292 (IQR: 2.130 ng/ml (0.54) vs. 2.124 ng/ml (1.68), p = 0.551). Similarly, serum SIRT1 levels did not differ between SIRT1 rs3758391 C/C genotype and C/T + T/T genotypes (IQR: 2.130 ng/ml (0.54) vs. 1.124 ng/ml (1.53), p = 1). No statistically significant difference was found between SIRT1 rs7895833 polymorphism A/A genotype and A/G + G/G genotypes (IQR: 2.130 ng/ml (0.51) vs. 2.130 ng/ml (1.57), p = 0.915).
No statistically significant difference in SIRT1 serum levels was found between subjects with A/A genotype and with A/G and G/G genotypes for SIRT1 rs3818292 (IQR: 2.174 ng/ml (1.51) vs. 1.911 ng/ml (1.85), respectively, p = 0.379). Serum SIRT1 levels did not differ between SIRT1 rs3758391 C/C genotype and C/T and T/T genotypes (IQR: 2.130 ng/ml (1.85) vs. 2.134 ng/ml (1.77), p = 0.525). In addition, there was no statistically significant difference in SIRT1 serum levels between the SIRT1 rs7895833 A/A genotype and the A/G + G/G genotypes (IQR: 2.130 ng/ml (1.85) vs. 2.134 ng/ml (1.77), p = 0.525.
No statistically significant differences in serum SIRT1 levels were found between subjects with A/A genotype and with A/G + G/G genotypes for the SIRT1 rs3818292 (IQR: 2.130 ng/ml (0.58) vs. 2.130 ng/ml (1.65), respectively, p = 0.910). Serum SIRT1 levels did not differ between SIRT1 rs3758391 C/C genotype and C/T and T/T genotypes (IQR: 2.066 ng/ml (0.55) vs. 2.188 ng/ml (1.26), respectively, p = 0.472). In addition, there was no statistically significant difference in SIRT1 serum levels between the SIRT1 rs7895833 A/A genotype and the A/G + G/G genotypes (IQR: 2.130 ng/ml (0.52) vs. 2.130 ng/ml (1.57), p = 0.424).