Background
Methods
Subjects
SNP selection and genotyping
SNP_ID | 1st-PCR primer | 2nd-PCR primer | UEP SEQ |
---|---|---|---|
rs3093203 | ACGTTGGATGAAAGCCACCAATCCGCTATG | ACGTTGGATGGGTCACATAGTGTACTGTCC | ACATAGTGTACTGTCCTTTTATA |
rs3093193 | ACGTTGGATGGTGATGAGACTAGTGATCCC | ACGTTGGATGGCCACATACACATTGATGGG | GTTTAGATAAACAGCCACA |
rs12459936 | ACGTTGGATGGGTAACCATCATTCTGCTTC | ACGTTGGATGAGAGGTCGCAGTAAGCTGAG | CAGCCTGGGTGACAGAG |
rs3093144 | ACGTTGGATGGGGAAGAATTGTGGCAAAGG | ACGTTGGATGAGGAGTCTCTCGTCCTTCTG | AGTTAAAAAAAAAATCCTAGATACTT |
rs3093110 | ACGTTGGATGGTCTCATTGATAAGAGGGAG | ACGTTGGATGTCCTGTTATGAGGGTACAGC | CCGTCTCCCACTTCCAC |
Statistical analysis
Results
Study participants
Characteristics | Cases N (%) | Controls N (%) | p-value |
---|---|---|---|
Number | 477 | 495 | |
Age,year (mean ± SD) | 60.05 ± 6.56 | 64.13 ± 10.82 | 0.000a |
> 61 | 274 (57.4%) | 212 (42.8%) | |
≤61 | 203 (42.6%) | 283 (57.2%) | |
Gender, no, % | 0.898b | ||
Male | 316 (66.2%) | 326 (65.9%) | |
Female | 161 (33.8%) | 169 (34.1%) | |
Triglycerides (mmol/L) | 1.78 ± 1.39 | 1.59 ± 1.06 | 0.051a |
Cholesterol (mmol/L) | 4.39 ± 1.20 | 3.93 ± 0.88 | 0.331 a |
HDL-C (mmol/L) | 0.92 ± 0.47 | 1.09 ± 0.26 |
< 0.001
a*
|
LDL-C (mmol/L) | 2.11 ± 1.76 | 1.81 ± 0.81 |
< 0.001
a*
|
The association between CYP4F2 gene and the risk of IS
SNP-ID | Chr | Gene | Position | Alleles | MAF | pa-HWE | OR (95% CI) | pb-value | |
---|---|---|---|---|---|---|---|---|---|
(minor/major) | cases | controls | |||||||
rs3093203 | 19 |
CYP4F2
| 15,878,374 | A/G | 0.235 | 0.227 | 0.608 | 1.04 (0.85–1.29) | 0.691 |
rs3093193 | 19 |
CYP4F2
| 15,881,104 | G/C | 0.324 | 0.287 | 0.584 | 1.19 (0.98–1.44) | 0.081 |
rs12459936 | 19 |
CYP4F2
| 15,882,231 | T/C | 0.412 | 0.462 | 0.470 | 0.82 (0.68–0.98) |
0.028*
|
rs3093144 | 19 |
CYP4F2
| 15,891,487 | T/C | 0.199 | 0.164 | 0.621 | 1.27 (1.01–1.60) |
0.043*
|
rs3093110 | 19 |
CYP4F2
| 15,896,974 | G/A | 0.127 | 0.126 | 0.839 | 1.01 (0.77–1.32) | 0.930 |
SNP-ID | Model | Genotype | No. (frequency) | Adjusteda | ||
---|---|---|---|---|---|---|
Case | Control | OR (95% CI) | pb-value | |||
rs3093203 | codominant | G/G | 275 (57.7%) | 292 (59.2%) | 1.00 | – |
A/G | 180 (37.7%) | 178 (36.1%) | 1.07 (0.82–1.41) | 0.614 | ||
A/A | 22 (4.6%) | 23 (4.7%) | 0.90 (0.48–1.69) | 0.737 | ||
dominant | G/G | 275 (57.7%) | 292 (59.2%) | 1.00 | – | |
A/G-A/A | 202 (42.3%) | 201 (40.8%) | 1.02 (0.82–1.27) | 0.868 | ||
recessive | G/G-A/G | 455 (95.4%) | 470 (95.3%) | 1.00 | – | |
A/A | 22 (4.6%) | 23 (4.7%) | 1.05 (0.81–1.37) | 0.706 | ||
log-additive | – | – | – | 0.87 (0.47–1.63) | 0.670 | |
rs3093193 | codominant | C/C | 216 (45.3%) | 248 (50.2%) | 1.00 | – |
G/C | 213 (44.7%) | 208 (42.1%) | 1.14 (0.87–1.50) | 0.342 | ||
G/G | 48 (10.01) | 38 (7.7%) | 1.39 (0.86–2.23) | 0.178 | ||
dominant | C/C | 216 (45.3%) | 248 (50.2%) | 1.00 | – | |
G/C-G/G | 261 (54.7%) | 246 (49.8%) | 1.16 (0.95–1.42) | 0.143 | ||
recessive | C/C-G/C | 429 (89.9%) | 456 (92.3%) | 1.00 | – | |
G/G | 48 (10.1%) | 38 (7.7%) | 1.18 (0.91–1.53) | 0.214 | ||
log-additive | – | – | – | 1.30 (0.82–2.05) | 0.259 | |
rs12459936 | codominant | C/C | 158 (33.5%) | 139 (28.1%) | 1.00 | – |
T/C | 238 (50.5%) | 254 (51.4%) | 0.89 (0.66–1.19) | 0.422 | ||
T/T | 75 (16.0%) | 101 (20.5%) | 0.71 (0.48–1.05) | 0.082 | ||
dominant | C/C | 158 (33.5%) | 139 (28.1%) | 1.00 | – | |
T/C-T/T | 313 (66.5%) | 355 (61.9%) | 0.85 (0.70–1.03) | 0.089 | ||
recessive | C/C-T/C | 396 (84.0%) | 393 (79.5%) | 1.00 | – | |
T/T | 75 (16.0%) | 101 (20.5%) | 0.84 (0.63–1.11) | 0.212 | ||
log-additive | – | – | – | 0.77 (0.55–1.08) | 0.123 | |
rs3093144 | codominant | C/C | 304 (64.0%) | 344 (69.5%) | 1.00 | – |
T/C | 153 (32.2%) | 140 (28.3%) | 1.18 (0.88–1.56) | 0.266 | ||
T/T | 18 (3.8%) | 11 (2.2%) | 1.95 (0.89–4.28) | 0.095 | ||
dominant | C/C | 304 (64.0%) | 344 (69.5%) | 1.00 | – | |
T/C-T/T | 171 (36.0%) | 151 (30.5%) | 1.24 (0.98–1.58) | 0.075 | ||
recessive | C/C-T/C | 457 (96.2%) | 484 (97.8%) | 1.00 | – | |
T/T | 18 (3.8%) | 11 (2.2%) | 1.23 (0.93–1.62) | 0.142 | ||
log-additive | – | – | – | 1.86 (0.85–4.05) | 0.120 | |
rs3093110 | codominant | A/A | 364 (76.3%) | 378 (76.5%) | 1.00 | – |
G/A | 105 (22.0%) | 108 (21.9%) | 1.01 (0.74–1.37) | 0.977 | ||
G/G | 8 (1.7%) | 8 (1.6%) | 1.00 (0.37–2.75) | 0.994 | ||
dominant | A/A | 304 (64.0%) | 344 (69.5%) | 1.00 | – | |
G/A-G/G | 171 (36.0%) | 151 (30.5%) | 1.00 (0.76–1.32) | 0.978 | ||
recessive | A/A-G/A | 469 (98.3%) | 486 (98.4%) | 1.00 | – | |
G/G | 8 (1.7%) | 8 (1.6%) | 1.01 (0.74–1.36) | 0.977 | ||
log-additive | – | – | – | 1.00 (0.37–2.74) | 0.996 |
Stratification analysis by age and gender
SNP | Model | Genotype | > 61 | ≤61 | Male | Female | ||||
---|---|---|---|---|---|---|---|---|---|---|
OR(95%CI) | p-value | OR(95%CI) | p-value | OR(95%CI) | p-value | OR(95%CI) | p-value | |||
rs3093193 | allele | C | 1.00 | 1.00 | 1.00 | 1.00 | ||||
G |
1.34 (1.02–1.77)
|
0.038
*
| 1.04 (0.79–1.37) | 0.791 |
1.35 (1.06–1.71)
|
0.016
*
| 0.95 (0.69–1.32) | 0.757 | ||
co-dominant | CC | 1.00 | – | 1.00 | – | 1.00 | – | 1.00 | – | |
GC | 1.56 (1.02–2.39) | 0.101 | 1.09 (0.74–1.61) | 0.657 | 1.10 (0.79–1.54) | 0.567 | 1.21 (0.76–1.92) | 0.421 | ||
GG | 1.86 (0.89–3.92) | 0.040 | 1.27 (0.64–2.50) | 0.494 |
2.29 (1.21–4.32)
|
0.011
*
| 0.64 (0.29–1.41) | 0.267 | ||
dominant | C/C | 1.00 | – | 1.00 | – | 1.00 | – | 1.00 | – | |
G/C-G/G |
1.61 (1.07–2.42)
|
0.022
*
| 1.12 (0.77–1.63) | 0.551 | 1.24 (0.90–1.71) | 0.195 | 1.08 (0.70–1.68) | 0.731 | ||
recessive | C/C-G/C | 1.00 | – | 1.00 | – | 1.00 | – | 1.00 | – | |
G/G | 1.50 (0.73–3.05) | 0.268 | 1.21 (0.63–2.33) | 0.560 |
2.19 (1.18–4.05)
|
0.013
*
| 0.58 (0.27–1.23) | 0.157 | ||
log-additive | – |
1.44 (1.05–1.98)
|
0.024
*
| 1.11 (0.83–1.49) | 0.472 |
1.31 (1.02–1.69)
|
0.036
*
| 0.93 (0.67–1.31) | 0.693 | |
rs12459936 | allele | C | 1.00 | 1.00 | 1.00 | |||||
T |
0.73 (0.56–0.94)
|
0.016
*
| 0.96 (0.74–1.23) | 0.727 |
0.78 (0.63–0.98)
|
0.031
*
| 0.89 (0.65–1.21) | 0.449 | ||
co-dominant | CC | 1.00 | – | 1.00 | – | 1.00 | – | 1.00 | – | |
TC | 0.70 (0.44–1.10) | 0.117 | 1.13 (0.73–1.75) | 0.582 | 0.94 (0.64–1.36) | 0.729 | 0.80 (0.49–1.31) | 0.383 | ||
TT |
0.48 (0.26–0.88)
|
0.018
*
| 0.79 (0.45–1.38) | 0.406 | 0.65 (0.40–1.05) | 0.079 | 0.86 (0.45–1.62) | 0.637 | ||
dominant | C/C | 1.00 | – | 1.00 | – | 1.00 | – | 1.00 | – | |
T/C-T/T |
0.63 (0.41–0.97)
|
0.036
*
| 1.03 (0.68–1.56) | 0.898 | 0.85 (0.60–1.22) | 0.380 | 0.82 (0.52–1.30) | 0.393 | ||
recessive | C/C-T/C | 1.00 | – | 1.00 | – | 1.00 | – | 1.00 | – | |
T/T | 0.59 (0.34–1.03) | 0.060 | 0.73 (0.45–1.17) | 0.189 | 0.68 (0.44–1.03) | 0.068 | 0.97 (0.55–1.72) | 0.922 | ||
log-additive | – |
0.69 (0.52–0.93)
|
0.015
*
| 0.91 (0.69–1.19) | 0.493 | 0.82 (0.65–1.04) | 0.103 | 0.91 (0.66–1.24) | 0.529 | |
rs3093144 | allele | C | 1.00 | 1.00 | 1.00 | 1.00 | ||||
T |
1.53 (1.09–2.14)
|
0.013
*
| 1.06 (0.76–1.48) | 0.741 |
1.36 (1.01–1.82)
|
0.040
*
| 1.13 (0.77–1.66) | 0.520 | ||
co-dominant | CC | 1.00 | – | 1.00 | – | 1.00 | – | 1.00 | – | |
TC | 1.54 (0.98–2.41) | 0.059 | 1.03 (0.68–1.55) | 0.890 | 1.15 (0.81–1.64) | 0.438 | 1.24 (0.77–2.00) | 0.383 | ||
TT | 2.57 (0.80–8.25) | 0.114 | 1.75 (0.58–5.31) | 0.324 |
4.5 (1.22–16.64)
|
0.024
*
| 0.93 (0.31–2.81) | 0.902 | ||
dominant | C/C | 1.00 | – | 1.00 | – | 1.00 | – | 1.00 | – | |
T/C-T/T |
1.62 (1.05–2.49)
|
0.029
*
| 1.08 (0.73–1.60) | 0.569 | 1.25 (0.89–1.77) | 0.198 | 1.20 (0.76–1.89) | 0.445 | ||
recessive | C/C-T/C | 1.00 | – | 1.00 | – | 1.00 | – | 1.00 | – | |
T/T | 2.25 (0.70–7.17) | 0.171 | 1.73 (0.58–5.22) | 0.328 |
4.32 (1.17–15.89)
|
0.028
*
| 0.87 (0.29–2.60) | 0.807 | ||
log-additive | – |
1.56 (1.07–2.27)
|
0.020
*
| 1.12 (0.79–1.58) | 0.522 | 1.34 (0.98–1.82) | 0.067 | 1.11 (0.76–1.64) | 0.579 |
Associations between haplotype analyses and IS risk
Block | Haplotype | Frequency | OR (95% CI) | p-value | |
---|---|---|---|---|---|
Case (477) | Control (495) | ||||
Block 1 | rs3093203|rs3093193|rs12459936|rs3093144|rs3093110 | ||||
GGCCG | 418 (87.7%) | 436 (88%) | 0.99 (0.75–1.31) | 0.944 | |
GGCTA | 94 (19.8%) | 80 (16.1%) | 1.25 (0.99–1.60) | 0.065 | |
GCTCA | 280 (58.8%) | 268 (54.1%) | 1.17 (0.97–1.41) | 0.109 | |
ACCCA | 111 (23.2%) | 111 (22.4%) | 1.02 (0.82–1.28) | 0.837 | |
GCCCA | 465 (97.4%) | 483 (97.5%) | 1.01 (0.57–1.81) | 0.970 |
Block | Haplotype | Frequency | OR (95% CI) | p-value | |
---|---|---|---|---|---|
Case(477) | Control(495) | ||||
Block 1 | rs3093193/rs12459936/rs3093144 | ||||
CTC | 196 (41.1%) | 228 (46%) | 1 | – | |
CCC | 124 (26.1%) | 125 (25.2%) | 1.12 (0.88–1.41) | 0.360 | |
GCT | 94 (19.7%) | 80 (16.2%) |
1.31 (1.01–1.70)
|
0.043
*
| |
GCC | (61 (12.7%) | 61 (12.3%) | 1.11 (0.83–1.49) | 0.490 |