Table 1Primer sequences for genotyping
Genes |
SNPs |
Primers |
Sequences (5'→3')
|
Annealing temp (c ) |
COMT |
rs4680 (Val158Met) |
Forward |
ATCAACCCCGACTGTGCC |
55 |
|
|
Reverse |
CTTTTTCCAGGTCTGACAACG |
|
|
|
Extension |
5'FAM -GCGGATGGTGGATTTCGCTGGC |
|
|
rs165599 (3'-fianking region) |
Forward |
TCCTGCAGCTAGGCCAGG |
55 |
|
|
Reverse |
AGAAAGGTGTGAATGCTGG |
|
|
|
Extension |
5'FAM -GCTGACTCCTCTTCGTTTCCCAGGC |
|
MTHFR |
rs1801133 (C677T) |
Forward |
AAGCAGGGAGCTTTGAGGC |
55 |
|
|
Reverse |
CAAGTGATGCCCATGTCG |
|
|
|
Extension |
5'FAM -GAAAAGCTGCGTGATGATGAAATCG |
|
|
rs1801131 (A1298C) |
Forward |
AAGGAGGAGCTGCTGAAGA |
55 |
|
|
Reverse |
TTTGTGACCATTCCGGTT |
|
|
|
Extension |
5'FAM -TAAAGAACAAAGACTTCAAAGACACTT |
|
Table 2Genotype frequencies of selected polymorphisms in COMT and MTHFR among cases and controls
Genes |
SNPs |
Genotype |
N (%)
|
OR |
95% CI |
|
p-value |
Controls (n=348)
|
Patients (n=360)
|
n |
% |
n |
% |
COMT |
rs4680 |
GG |
192 |
55.2 |
194 |
53.9 |
1.00* |
- |
- |
- |
|
|
GA |
132 |
37.9 |
139 |
38.6 |
1.04 |
0.76 |
1.42 |
0.79 |
|
|
AA |
24 |
6.9 |
27 |
7.5 |
1.11 |
0.62 |
2.00 |
0.72 |
|
rs165599 |
GG |
76 |
21.8 |
66 |
18.3 |
1.00* |
- |
- |
- |
|
|
GA |
160 |
46.0 |
184 |
51.1 |
1.32 |
0.89 |
1.96 |
0.16 |
|
|
AA |
112 |
32.2 |
110 |
30.6 |
1.13 |
0.74 |
1.72 |
0.57 |
MTHFR |
rs1801133 |
CC |
130 |
37.4 |
125 |
34.7 |
1.00* |
- |
- |
- |
|
|
CT |
158 |
45.4 |
176 |
48.9 |
1.16 |
0.84 |
1.61 |
0.38 |
|
|
TT |
60 |
17.2 |
59 |
16.4 |
1.02 |
0.66 |
1.60 |
0.92 |
|
rs1801131 |
AA |
239 |
68.7 |
248 |
68.9 |
1.00* |
- |
- |
- |
|
|
CA |
100 |
28.7 |
105 |
29.2 |
1.01 |
0.73 |
1.40 |
0.94 |
|
|
CC |
9 |
2.6 |
7 |
1.9 |
0.75 |
0.28 |
2.05 |
0.57 |
Table 3Stratified analysis by gender for the association between selected polymorphisms in COMT and MTHFR and schizophrenia risk
Genes |
SNPs |
Sex |
Genotype |
N (%)
|
OR |
95% CI |
p-vaiue |
Controls (n=348)
|
Patients (n=360)
|
n |
% |
n |
% |
COMT |
rs4680 |
Male |
GG |
114 |
58.2 |
105 |
53.8 |
1.00* |
- |
- |
- |
|
|
|
GA |
66 |
33.7 |
75 |
38.5 |
1.23 |
0.81 |
1.86 |
0.33 |
|
|
|
AA |
16 |
8.2 |
15 |
7.7 |
1.02 |
0.49 |
2.16 |
0.96 |
|
rs165599 |
|
GG |
40 |
20.4 |
35 |
17.9 |
1.00* |
- |
- |
- |
|
|
|
GA |
86 |
43.9 |
107 |
54.9 |
1.42 |
0.83 |
2.43 |
0.18 |
|
|
|
AA |
70 |
35.7 |
53 |
27.2 |
0.87 |
0.49 |
1.54 |
0.62 |
MTHFR |
rs1801133 |
|
CC |
79 |
40.3 |
71 |
36.4 |
1.00* |
- |
- |
- |
|
|
|
CT |
81 |
41.3 |
88 |
45.1 |
1.21 |
0.78 |
1.88 |
0.40 |
|
|
|
TT |
36 |
18.4 |
36 |
18.5 |
1.11 |
0.63 |
1.95 |
0.71 |
|
rs1801131 |
|
AA |
134 |
68.4 |
140 |
71.8 |
1.00* |
- |
- |
- |
|
|
|
CA |
58 |
29.6 |
51 |
26.2 |
0.84 |
0.54 |
1.31 |
0.45 |
|
|
|
CC |
4 |
2.0 |
4 |
2.1 |
0.96 |
0.24 |
3.91 |
0.95 |
COMT |
rs4680 |
Female |
GG |
78 |
51.3 |
89 |
54.3 |
1.00* |
- |
- |
- |
|
|
|
GA |
66 |
43.4 |
63 |
38.4 |
0.84 |
0.53 |
1.33 |
0.45 |
|
|
|
AA |
8 |
5.3 |
12 |
7.3 |
1.32 |
0.51 |
3.38 |
0.57 |
|
rs165599 |
|
GG |
36 |
23.7 |
30 |
18.3 |
1.00* |
- |
- |
- |
|
|
|
GA |
74 |
48.7 |
77 |
47.0 |
1.25 |
0.70 |
2.23 |
0.45 |
|
|
|
AA |
42 |
27.6 |
57 |
34.8 |
1.63 |
0.88 |
3.05 |
0.13 |
MTHFR |
rs1801133 |
|
CC |
51 |
33.6 |
54 |
32.9 |
1.00* |
- |
- |
- |
|
|
|
CT |
77 |
50.7 |
87 |
53.0 |
1.07 |
0.65 |
1.74 |
0.80 |
|
|
|
TT |
24 |
15.8 |
23 |
14.0 |
0.91 |
0.46 |
1.80 |
0.78 |
|
rs1801131 |
|
AA |
105 |
69.1 |
107 |
65.2 |
1.00* |
- |
- |
- |
|
|
|
CA |
42 |
27.6 |
54 |
32.9 |
1.26 |
0.78 |
2.05 |
0.35 |
|
|
|
CC |
5 |
3.3 |
3 |
1.8 |
0.59 |
0.14 |
2.53 |
0.48 |
Table 4Distribution of combined genotypes of COMT Val158Met, rs165599 and MTHFR C677T, A1298C among cases and controls
Genes |
Genotype |
|
N (%)
|
OR |
95% CI |
p-vaiue |
Controis (n=348)
|
Patients (n=360)
|
COMT |
rs4680 |
rs165599 |
n |
% |
n |
% |
|
|
|
|
|
|
|
|
|
|
|
Vai |
GG |
65 |
33.9 |
57 |
29.4 |
1.00* |
- |
- |
- |
|
|
GA |
85 |
44.3 |
100 |
51.5 |
1.34 |
0.85 |
2.12 |
0.20 |
|
|
AA |
42 |
21.9 |
37 |
19.1 |
1.01 |
0.57 |
1.77 |
0.99 |
|
Met carrier |
GG |
11 |
7.1 |
9 |
5.4 |
1.00* |
- |
- |
- |
|
|
GA |
75 |
48.1 |
84 |
50.6 |
1.37 |
0.54 |
3.48 |
0.51 |
|
|
AA |
70 |
44.9 |
73 |
44.0 |
1.27 |
0.50 |
3.26 |
0.61 |
|
|
|
|
|
|
MTHFR |
rs1801133 |
rs1801131 |
n |
% |
n |
% |
|
|
|
|
|
|
|
|
|
|
|
CC |
AA |
72 |
55.4 |
63 |
50.4 |
1.00* |
- |
- |
- |
|
|
CA |
50 |
38.5 |
55 |
44.0 |
1.26 |
0.75 |
2.10 |
0.38 |
|
|
CC |
8 |
6.2 |
7 |
5.6 |
1.00 |
0.34 |
2.91 |
1.00 |
|
CT+TT |
AA |
167 |
76.6 |
185 |
78.7 |
1.00* |
- |
- |
- |
|
|
CA |
50 |
22.9 |
50 |
21.3 |
0.90 |
0.58 |
1.41 |
0.65 |
|
|
CC |
1 |
0.5 |
0 |
0 |
- |
- |
- |
- |
Table 5Interactive effects between COMT Val158Met and MTHFR C677T on schizophrenia risk
Genes |
|
MTHFRrs1801133 |
N (%)
|
OR |
95% CI |
p-vaiue |
Controis (n=348)
|
Patients (n=360)
|
n |
% |
n |
% |
COMT |
Vai |
CC |
69 |
35.9 |
62 |
32.0 |
1.00* |
- |
- |
- |
rs4680 |
|
CT |
97 |
50.5 |
100 |
51.5 |
1.15 |
0.74 |
1.79 |
0.54 |
|
|
TT |
26 |
13.5 |
32 |
16.5 |
1.37 |
0.74 |
2.55 |
0.32 |
|
Met carrier |
CC |
61 |
39.1 |
63 |
38.0 |
1.00* |
- |
- |
- |
|
|
CT |
61 |
39.1 |
76 |
45.8 |
1.21 |
0.74 |
1.96 |
0.45 |
|
|
TT |
34 |
21.8 |
27 |
16.3 |
0.77 |
0.42 |
1.42 |
0.40 |