Introduction
Methods
Ethical statement
Study population
Inclusion and exclusion criteria
Information collection
SNPs selection and genotyping
Statistical analysis
Variables | Control group (n = 652) | Case group (n = 569) | Univariable analysis |
---|---|---|---|
Demographic characteristics | |||
Maternal age (years) | 28.60 ± 4.75 | 28.23 ± 5.07 | |
< 35 | 560 (85.9%) | 494 (86.8%) | χ2 = 0.222; P = 0.637 |
≥ 35 | 92 (14.1%) | 75 (13.2%) | |
Education level | |||
Less than primary or primary | 9 (1.4%) | 85 (14.9%) | Z = -14.298; P = 0.000* |
Junior high school | 127 (19.5%) | 231 (40.6%) | |
Senior middle school | 210 (32.2%) | 162 (28.5%) | |
College and above | 306 (46.9%) | 91 (16.0%) | |
Family income in the past 1 year (RMB) | |||
≤ 50,000 | 187 (28.7%) | 463 (81.4%) | Z = -18.157; P = 0.000* |
50,000–100,000 | 275 (42.2%) | 77 (13.5%) | |
100,000–150,000 | 59 (9.0%) | 11 (1.9%) | |
> 150,000 | 131 (20.1%) | 18 (3.2%) | |
Body mass index before this pregnancy | |||
< 18.5 | 149 (22.8%) | 125 (22.0%) | χ2 = 0.204; P = 0.903 |
18.5–23.99 | 391 (60.0%) | 342 (60.1%) | |
≥ 24 | 112 (17.2%) | 102 (17.9%) | |
Residence location (rural areas) | 349 (53.5%) | 428 (75.2%) | χ2 = 61.784; P = 0.000 |
Abnormal pregnancy history before this pregnancy | |||
Spontaneous abortion (yes) | 55 (8.4%) | 68 (12.0%) | χ2 = 4.144; P = 0.042 |
Induced abortion or labor (yes) | 208 (31.9%) | 242 (42.5%) | χ2 = 14.750; P = 0.000 |
Fetal death or stillbirth (yes) | 2 (0.3%) | 19 (3.3%) | χ2 = 16.530; P = 0.000 |
Premature delivery (yes) | 4 (0.6%) | 8 (1.4%) | χ2 = 1.961; P = 0.161 |
Low birth weight (yes) | 3 (0.5%) | 5 (0.9%) | χ2 = 0.818; P = 0.366 |
Neonatal death (yes) | 0 | 7 (1.2%) | P = 0.005** |
Ectopic pregnancy (yes) | 18 (2.8%) | 12 (2.1%) | χ2 = 0.539; P = 0.463 |
Hypertension of pregnancy (yes) | 12 (1.8%) | 39 (6.9%) | χ2 = 19.082; P = 0.000 |
Gestational diabetes mellitus (yes) | 23 (3.5%) | 59 (10.4%) | χ2 = 22.701; P = 0.000 |
Family history | |||
Consanguineous marriages (yes) | 2 (0.3%) | 24 (4.2%) | χ2 = 22.302; P = 0.000 |
Congenital malformations (yes) | 4 (0.6%) | 40 (7.0%) | χ2 = 36.010; P = 0.000 |
Personal lifestyle and habit before this pregnancy in the 3 months before this pregnancy | |||
Active smoking (yes) | 12 (1.8%) | 46 (8.1%) | χ2 = 26.180; P = 0.000 |
Passive smoking (yes) | 249 (38.2%) | 293 (51.5%) | χ2 = 21.785; P = 0.000 |
Drinking (yes) | 45 (6.9%) | 78 (13.7%) | χ2 = 15.538; P = 0.000 |
Drinking tea (yes) | 128 (19.6%) | 77 (13.5%) | χ2 = 8.091; P = 0.004 |
Exposure history of environmental hazardous substance in the 3 months before this pregnancy | |||
Harmful chemicals (yes) | 42 (6.4%) | 119 (20.9%) | χ2 = 55.592; P = 0.000 |
Noise pollution exposure (yes) | 121 (18.6%) | 152 (26.7%) | χ2 = 11.641; P = 0.000 |
Newly renovated houses (yes) | 37 (5.7%) | 44 (7.7%) | χ2 = 2.078; P = 0.149 |
Dyeing or perming hair (yes) | 42 (6.4%) | 70 (12.3%) | χ2 = 12.526; P = 0.000 |
Frequency of cosmetics use | |||
Never | 409 (62.7%) | 418 (73.5%) | Z = -3.106; P = 0.002* |
Sometime | 160 (24.5%) | 66 (11.6%) | |
Often | 37 (5.7%) | 36 (6.3%) | |
Every day | 46 (7.1%) | 49 (8.6%) | |
Medicine history in this pregnancy | |||
Folate use (no) | 44 (6.7%) | 95 (16.7%) | χ2 = 29.803; P = 0.000 |
Macrolide antibiotics (yes) | 23 (3.6%) | 35 (6.2%) | χ2 = 4.622; P = 0.032 |
Antidepressants (yes) | 2 (0.3%) | 10 (1.8%) | χ2 = 6.571; P = 0.010 |
Results
Characteristics of study participants
Association of maternal MTHFR gene polymorphisms with the risk of CHD in offspring
SNPs | Chromosome | Major allele | Minor allele | MAF | group | Genotype frequencies† | HWE test P | ||
---|---|---|---|---|---|---|---|---|---|
AA | AB | BB | |||||||
rs2274976 | 1:11790870 | C | T | 0.1183 | Control | 505 (77.5%) | 136 (20.9%) | 11 (1.7%) | 0.5995 |
Case | 448 (78.7%) | 111 (19.5%) | 10 (1.8%) | ||||||
rs1801133 | 1:11796321 | G | A | 0.3141 | Control | 308 (47.2%) | 289 (44.3%) | 55 (8.4%) | 0.2651 |
Case | 245 (43.1%) | 280 (49.2%) | 44 (7.7%) | ||||||
rs535107 | 1:11829411 | A | G | 0.2404 | Control | 402 (61.7%) | 216 (33.1%) | 34 (5.2%) | 0.4798 |
Case | 314 (55.2%) | 207 (36.4%) | 48 (8.4%) | ||||||
rs4846052 | 1:11797894 | C | T | 0.1057 | Control | 567 (87.0%) | 79 (12.1%) | 6 (0.9%) | 0.0884 |
Case | 437 (76.8%) | 97 (17.0%) | 35 (6.2%) | ||||||
rs1476413 | 1:11792243 | C | T | 0.2391 | Control | 399 (61.2%) | 217 (33.3%) | 36 (5.5%) | 0.3668 |
Case | 330 (58.0%) | 183 (32.2%) | 56 (9.8%) | ||||||
rs4846048 | 1:11786195 | A | G | 0.1212 | Control | 522 (80.1%) | 119 (18.3%) | 11 (1.7%) | 0.1703 |
Case | 433 (76.1%) | 117 (20.6%) | 19 (3.3%) | ||||||
rs4846051 | 1:11794400 | A | G | 0.0020 | Control | 649 (99.5%) | 3 (0.5%) | 0 | 0.9530 |
Case | 567 (99.6%) | 2 (0.4%) | 0 | ||||||
rs1931226 | 1:11803917 | C | T | 0.0012 | Control | 649 (99.5%) | 3 (0.5%) | 0 | 0.9530 |
Case | 569 (100.0%) | 0 | 0 | ||||||
rs2066470 | 1:11803000 | G | A | 0.1167 | Control | 517 (79.3%) | 126 (19.3%) | 9 (1.4%) | 0.0606 |
Case | 443 (77.9%) | 111 (19.5%) | 15 (2.6%) | ||||||
rs3737964 | 1:11806987 | C | T | 0.1200 | Control | 523 (80.2%) | 118 (18.1%) | 11 (1.7%) | 0.1544 |
Case | 430 (75.6%) | 125 (22.0%) | 14 (2.5%) | ||||||
rs7525338 | 1:11802275 | C | T | 0.0020 | Control | 649 (99.5%) | 3 (0.5%) | 0 | 0.9530 |
Case | 567 (99.6%) | 2 (0.4%) | 0 | ||||||
rs1801131 | 1:11794419 | T | G | 0.2138 | Control | 448 (68.7%) | 188 (28.8%) | 16 (2.5%) | 0.4750 |
Case | 323 (56.8%) | 190 (33.4%) | 56 (9.8%) | ||||||
rs1889292 | 1:11780886 | C | T | 0.2445 | Control | 377 (57.8%) | 246 (37.7%) | 29 (4.4%) | 0.1586 |
Case | 318 (55.9%) | 209 (36.7%) | 42 (7.4%) |
SNPs | Total CHD† | ASD† | VSD† | PDA† | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
ORadj (95%CI) | P | FDR_P | ORadj (95%CI) | P | FDR_P | ORadj (95%CI) | P | FDR_P | ORadj (95%CI) | P | FDR_P | |
rs2274976 | ||||||||||||
CC | 1 | 1 | 1 | 1 | ||||||||
CT | 0.83 (0.61–1.14) | 0.254 | 0.462 | 0.98 (0.57–1.67) | 0.928 | 0.999 | 0.79 (0.56–1.12) | 0.184 | 0.409 | 0.53 (0.31–0.89) | 0.017 | 0.113 |
TT | 1.01 (0.36–2.80) | 0.987 | 0.987 | - | 0.999 | 0.999 | 1.39 (0.50–3.86) | 0.534 | 0.763 | 1.26 (0.39–4.12) | 0.699 | 0.873 |
Dominant model | 0.84 (0.62–1.15) | 0.278 | 0.397 | 0.92 (0.54–1.58) | 0.768 | 0.913 | 0.83 (0.59–1.16) | 0.267 | 0.445 | 0.59 (0.37–0.96) | 0.033 | 0.083 |
Recessive model | 1.05 (0.38–2.91) | 0.925 | 0.925 | - | 0.999 | 0.999 | 1.45 (0.52–4.03) | 0.473 | 0.676 | 1.37 (0.42–4.48) | 0.606 | 0.673 |
Additive model | 0.87 (0.66–1.15) | 0.341 | 0.426 | 0.88 (0.53–1.45) | 0.606 | 0.895 | 0.89 (0.66–1.20) | 0.428 | 0.653 | 0.70 (0.46–1.06) | 0.090 | 0.180 |
rs1801133 | ||||||||||||
GG | 1 | 1 | 1 | 1 | ||||||||
GA | 1.28 (0.98–1.66) | 0.072 | 0.240 | 1.46 (0.91–2.35) | 0.120 | 0.400 | 1.35 (1.01–1.81) | 0.041 | 0.205 | 1.52 (1.03–2.24) | 0.034 | 0.125 |
AA | 1.22 (0.76–1.97) | 0.410 | 0.547 | 1.75 (0.79–3.86) | 0.166 | 0.463 | 1.05 (0.62–1.78) | 0.852 | 0.949 | 0.89 (0.38–2.10) | 0.786 | 0.873 |
Dominant model | 1.27 (0.98–1.63) | 0.069 | 0.230 | 1.50 (0.95–2.37) | 0.079 | 0.225 | 1.30 (0.99–1.72) | 0.064 | 0.213 | 1.44 (0.98–2.11) | 0.060 | 0.120 |
Recessive model | 1.08 (0.68–1.70) | 0.742 | 0.824 | 1.45 (0.69–3.08) | 0.329 | 0.823 | 0.90 (0.55–1.49) | 0.687 | 0.859 | 0.71 (0.31–1.62) | 0.412 | 0.515 |
Additive model | 1.17 (0.96–1.43) | 0.115 | 0.192 | 1.37 (0.97–1.93) | 0.072 | 0.240 | 1.15 (0.93–1.43) | 0.201 | 0.503 | 1.21 (0.89–1.63) | 0.228 | 0.285 |
rs535107 | ||||||||||||
AA | 1 | 1 | 1 | 1 | ||||||||
AG | 1.16 (0.88–1.52) | 0.285 | 0.407 | 1.53 (0.95–2.44) | 0.078 | 0.400 | 1.03 (0.76–1.39) | 0.854 | 0.949 | 1.15 (0.78–1.70) | 0.472 | 0.640 |
GG | 1.55 (0.93–2.59) | 0.096 | 0.274 | 1.23 (0.48–3.15) | 0.672 | 0.999 | 1.64 (0.96–2.80) | 0.073 | 0.243 | 1.54 (0.78–3.05) | 0.213 | 0.387 |
Dominant model | 1.22 (0.94–1.57) | 0.135 | 0.270 | 1.48 (0.94–2.33) | 0.090 | 0.225 | 1.12 (0.85–1.48) | 0.437 | 0.568 | 1.22 (0.84–1.75) | 0.298 | 0.373 |
Recessive model | 1.47 (0.89–2.43) | 0.138 | 0.230 | 1.02 (0.41–2.56) | 0.967 | 0.999 | 1.62 (0.96–2.74) | 0.073 | 0.168 | 1.46 (0.75–2.83) | 0.265 | 0.515 |
Additive model | 1.20 (0.98–1.48) | 0.074 | 0.247 | 1.29 (0.90–1.84) | 0.166 | 0.415 | 1.16 (0.93–1.45) | 0.178 | 0.503 | 1.20 (0.91–1.60) | 0.201 | 0.285 |
rs4846052 | ||||||||||||
CC | 1 | 1 | 1 | 1 | ||||||||
CT | 1.56 (1.09–2.24) | 0.015 | 0.100 | 1.64 (0.89–2.99) | 0.110 | 0.400 | 1.28 (0.86–1.90) | 0.219 | 0.438 | 0.94 (0.54–1.64) | 0.831 | 0.875 |
TT | 7.62 (2.95–19.65) | 0.000 | 0.000 | 7.56 (2.39–23.90) | 0.001 | 0.020 | 5.12 (1.92–13.65) | 0.001 | 0.010 | 6.57 (2.34–18.44) | 0.000 | 0.000 |
Dominant model | 1.97 (1.41–2.75) | 0.000 | 0.000 | 2.14 (1.25–3.66) | 0.006 | 0.060 | 1.56 (1.09–2.24) | 0.016 | 0.080 | 1.40 (0.87–2.24) | 0.165 | 0.236 |
Recessive model | 7.12 (2.76–18.33) | 0.000 | 0.000 | 7.04 (2.23–22.16) | 0.001 | 0.010 | 4.93 (1.85–13.13) | 0.001 | 0.005 | 6.63 (2.37–18.54) | 0.000 | 0.000 |
Additive model | 1.96 (1.48–2.60) | 0.000 | 0.000 | 2.14 (1.39–3.28) | 0.001 | 0.010 | 1.62 (1.20–2.19) | 0.002 | 0.010 | 1.61 (1.12–2.32) | 0.011 | 0.050 |
rs1476413 | ||||||||||||
CC | 1 | 1 | 1 | 1 | ||||||||
CT | 0.97 (0.74–1.28) | 0.819 | 0.862 | 1.25 (0.79–1.98) | 0.349 | 0.635 | 0.71 (0.52–0.97) | 0.031 | 0.205 | 0.86 (0.58–1.30) | 0.480 | 0.640 |
TT | 1.50 (0.92–2.45) | 0.107 | 0.268 | 0.37 (0.09–1.61) | 0.185 | 0.463 | 1.62 (0.97–2.72) | 0.065 | 0.243 | 1.72 (0.92–3.21) | 0.091 | 0.184 |
Dominant model | 1.05 (0.81–1.36) | 0.704 | 0.880 | 1.12 (0.71–1.76) | 0.623 | 0.890 | 0.85 (0.64–1.13) | 0.255 | 0.445 | 1.01 (0.69–1.46) | 0.978 | 0.978 |
Recessive model | 1.52 (0.94–2.46) | 0.091 | 0.227 | 0.34 (0.08–1.45) | 0.144 | 0.480 | 1.82 (1.09–3.01) | 0.021 | 0.070 | 1.81 (0.98–3.32) | 0.057 | 0.173 |
Additive model | 1.11 (0.91–1.35) | 0.314 | 0.449 | 0.97 (0.66–1.41) | 0.862 | 0.895 | 1.01 (0.81–1.26) | 0.910 | 0.910 | 1.13 (0.85–1.49) | 0.399 | 0.443 |
rs4846048 | ||||||||||||
AA | 1 | 1 | 1 | 1 | ||||||||
AG | 1.09 (0.79–1.50) | 0.622 | 0.732 | 1.14 (0.67–1.94) | 0.635 | 0.999 | 1.13 (0.80–1.60) | 0.484 | 0.755 | 1.45 (0.94–2.24) | 0.092 | 0.184 |
GG | 2.50 (1.11–5.63) | 0.027 | 0.135 | - | 0.999 | 0.999 | 0.99 (0.37–2.69) | 0.991 | 0.992 | 2.64 (1.00–6.95) | 0.050 | 0.125 |
Dominant model | 1.20 (0.89–1.63) | 0.239 | 0.398 | 1.04 (0.61–1.77) | 0.878 | 0.913 | 1.12 (0.80–1.56) | 0.511 | 0.568 | 1.57 (1.05–2.37) | 0.029 | 0.083 |
Recessive model | 2.46 (1.09–5.54) | 0.030 | 0.100 | - | 0.999 | 0.999 | 0.97 (0.36–2.63) | 0.956 | 0.956 | 2.44 (0.93–6.38) | 0.069 | 0.173 |
Additive model | 1.26 (0.97–1.63) | 0.085 | 0.170 | 0.95 (0.58–1.55) | 0.829 | 0.895 | 1.09 (0.81–1.45) | 0.575 | 0.653 | 1.53 (1.09–2.14) | 0.015 | 0.050 |
rs2066470 | ||||||||||||
GG | 1 | 1 | 1 | 1 | ||||||||
GA | 0.90 (0.65–1.24) | 0.505 | 0.631 | 1.35 (0.81–2.27) | 0.251 | 0.502 | 0.92 (0.64–1.30) | 0.628 | 0.794 | 0.60 (0.36–0.99) | 0.048 | 0.125 |
AA | 1.74 (0.65–4.66) | 0.272 | 0.418 | - | 0.999 | 0.999 | 2.26 (0.87–5.86) | 0.093 | 0.266 | 1.21 (0.34–4.27) | 0.767 | 0.873 |
Dominant model | 0.95 (0.69–1.29) | 0.727 | 0.808 | 1.25 (0.75–2.09) | 0.395 | 0.688 | 1.00 (0.72–1.40) | 0.995 | 0.995 | 0.65 (0.40–1.04) | 0.075 | 0.125 |
Recessive model | 1.78 (0.67–4.75) | 0.252 | 0.360 | - | 0.999 | 0.999 | 2.31 (0.89–5.96) | 0.084 | 0.168 | 1.29 (0.37–4.57) | 0.690 | 0.690 |
Additive model | 1.00 (0.76–1.32) | 0.983 | 0.983 | 1.12 (0.70–1.80) | 0.643 | 0.895 | 1.08 (0.81–1.45) | 0.588 | 0.653 | 0.74 (0.49–1.12) | 0.150 | 0.250 |
rs3737964 | ||||||||||||
CC | 1 | 1 | 1 | 1 | ||||||||
CT | 1.26 (0.92–1.73) | 0.154 | 0.308 | 1.37 (0.81–2.34) | 0.242 | 0.502 | 1.13 (0.80–1.61) | 0.481 | 0.755 | 1.63 (1.05–2.54) | 0.030 | 0.125 |
TT | 1.66 (0.69–3.96) | 0.257 | 0.428 | - | 0.999 | 0.999 | 1.00 (0.37–2.69) | 0.992 | 0.992 | 1.74 (0.61–4.99) | 0.303 | 0.505 |
Dominant model | 1.30 (0.95–1.76) | 0.097 | 0.243 | 1.25 (0.74–2.11) | 0.413 | 0.688 | 1.12 (0.80–1.57) | 0.509 | 0.568 | 1.65 (1.08–2.50) | 0.020 | 0.083 |
Recessive model | 1.58 (0.66–3.78) | 0.300 | 0.375 | - | 0.999 | 0.999 | 0.97 (0.36–2.63) | 0.956 | 0.956 | 1.58 (0.55–4.50) | 0.396 | 0.515 |
Additive model | 1.27 (0.97–1.65) | 0.079 | 0.198 | 1.10 (0.68–1.77) | 0.707 | 0.895 | 1.09 (0.81–1.46) | 0.575 | 0.653 | 1.50 (1.05–2.13) | 0.025 | 0.063 |
rs1801131 | ||||||||||||
TT | 1 | 1 | 1 | 1 | ||||||||
TG | 1.30 (0.98–1.71) | 0.067 | 0.268 | 1.48 (0.92–2.39) | 0.105 | 0.400 | 1.12 (0.82–1.52) | 0.491 | 0.755 | 1.48 (1.00–2.18) | 0.050 | 0.125 |
GG | 5.18 (2.77–9.71) | 0.000 | 0.000 | 4.55 (1.67–12.34) | 0.003 | 0.030 | 4.98 (2.66–9.33) | 0.000 | 0.000 | 3.65 (1.63–8.18) | 0.002 | 0.020 |
Dominant model | 1.58 (1.22–2.06) | 0.001 | 0.005 | 1.68 (1.07–2.65) | 0.025 | 0.125 | 1.43 (1.08–1.90) | 0.014 | 0.080 | 1.66 (1.14–2.40) | 0.008 | 0.080 |
Recessive model | 4.76 (2.56–8.85) | 0.000 | 0.000 | 3.99 (1.49–10.71) | 0.006 | 0.030 | 4.82 (2.59–8.98) | 0.000 | 0.000 | 3.18 (1.44–7.02) | 0.004 | 0.020 |
Additive model | 1.68 (1.36–2.09) | 0.000 | 0.000 | 1.75 (1.19–2.56) | 0.004 | 0.020 | 1.59 (1.27–1.99) | 0.000 | 0.000 | 1.67 (1.23–2.26) | 0.001 | 0.010 |
rs1889292 | ||||||||||||
CC | 1 | 1 | 1 | 1 | ||||||||
CT | 0.96 (0.73–1.25) | 0.742 | 0.824 | 0.98 (0.62–1.56) | 0.933 | 0.999 | 0.80 (0.60–1.08) | 0.139 | 0.348 | 0.98 (0.67–1.43) | 0.903 | 0.903 |
TT | 1.49 (0.86–2.59) | 0.152 | 0.338 | 0.93 (0.31–2.82) | 0.902 | 0.999 | 1.16 (0.64–2.11) | 0.635 | 0.794 | 1.40 (0.67–2.93) | 0.368 | 0.566 |
Dominant model | 1.02 (0.79–1.32) | 0.892 | 0.892 | 0.98 (0.62–1.53) | 0.913 | 0.913 | 0.84 (0.64–1.12) | 0.230 | 0.445 | 1.03 (0.71–1.48) | 0.881 | 0.978 |
Recessive model | 1.52 (0.89–2.60) | 0.128 | 0.256 | 0.94 (0.32–2.80) | 0.912 | 0.999 | 1.26 (0.70–2.27) | 0.441 | 0.676 | 1.42 (0.69–2.91) | 0.342 | 0.515 |
Additive model | 1.08 (0.88–1.33) | 0.477 | 0.530 | 0.98 (0.66–1.43) | 0.895 | 0.895 | 0.92 (0.73–1.16) | 0.490 | 0.653 | 1.08 (0.80–1.45) | 0.619 | 0.619 |
Linkage disequilibrium test and haplotype analysis
Haplotypes | Controls (%) | Cases (%) | OR (95% CI)† | P |
---|---|---|---|---|
Total CHD group versus the control group | ||||
rs4846048-rs2274976 | ||||
A–C | 1007.3 (77.2) | 853.5 (75.0) | 1 | |
G–C | 138.7 (10.6) | 153.5 (13.5) | 1.31 (1.02–1.67) | 0.034 |
A–T | 155.7 (11.9) | 129.5 (11.4) | 0.98 (0.76–1.26) | 0.884 |
rs1801133-rs4846052 | ||||
G–C | 816.3 (62.6) | 609.3 (53.5) | 1 | |
A–C | 396.7 (30.4) | 361.7 (31.8) | 1.22 (1.02–1.46) | 0.027 |
G–T | 88.7 (6.8) | 160.7 (14.1) | 2.43 (1.84–3.21) | < 0.001 |
rs2066470-rs3737964-rs535107 | ||||
G–C–A | 979.8 (75.1) | 832.5 (73.2) | 1 | |
G–T–G | 112.2 (8.6) | 152.6 (13.4) | 1.60 (1.23–2.08) | < 0.001 |
A–C–G | 117.0 (9.0) | 138.6 (12.2) | 1.39 (1.07–1.81) | 0.013 |
G–C–G | 47.5 (3.6) | 11.6 (1.0) | 0.29 (0.15–0.55) | < 0.001 |
The ASD group versus the control group | ||||
rs4846048-rs2274976 | ||||
A–C | 1007.4 (77.3) | 146.4 (77.1) | 1 | |
A–T | 155.6 (11.9) | 20.6 (10.8) | 0.91 (0.56–1.49) | 0.710 |
G–C | 138.6 (10.6) | 22.6 (11.9) | 1.12 (0.70–1.81) | 0.636 |
rs1801131-rs1801133-rs4846052 | ||||
T–G–C | 687.7 (52.7) | 73.1 (38.5) | 1 | |
T–A–C | 388.1 (29.8) | 59.7 (31.4) | 1.45 (1.01–2.08) | 0.046 |
G–G–C | 137.2 (10.5) | 26.2 (13.8) | 1.80 (1.11–2.91) | 0.017 |
G–G–T | 74.5 (5.7) | 22.1 (11.6) | 2.79 (1.64–4.75) | < 0.001 |
rs2066470-rs3737964 | ||||
G–C | 1025.9 (78.7) | 142.0 (74.7) | 1 | |
A–C | 138.1 (10.6) | 24.0 (12.7) | 1.26 (0.79–2.00) | 0.340 |
G–T | 134.1 (10.3) | 23.0 (12.1) | 1.24 (0.77–1.99) | 0.377 |
The VSD group versus the control group | ||||
rs4846048-rs2274976 | ||||
A–C | 1007.4 (77.3) | 535.5 (75.0) | 1 | |
A–T | 155.6 (11.9) | 81.5 (13.5) | 0.99 (0.74–1.31) | 0.920 |
G–C | 138.6 (10.6) | 87.5 (11.4) | 1.19 (0.89–1.58) | 0.241 |
rs1801133-rs4846052 | ||||
G–C | 814.0 (62.4) | 378.0 (53.5) | 1 | |
A–C | 399.0 (30.6) | 232.0 (31.8) | 1.25 (1.02–1.53) | 0.030 |
G–T | 91.0 (7.0) | 96.0 (14.1) | 2.27 (1.66–3.10) | < 0.001 |
rs2066470-rs3737964 | ||||
G–C | 1025.8 (78.7) | 530.4 (73.2) | 1 | |
A–C | 138.2 (10.6) | 87.6 (12.2) | 1.23 (0.92–1.63) | 0.165 |
G–T | 134.2 (10.3) | 84.6 (1.0) | 1.22 (0.91–1.63) | 0.183 |
The PDA group versus the control group | ||||
rs4846048-rs2274976 | ||||
A–C | 1007.3 (77.2) | 246.4 (72.5) | 1 | |
G–C | 138.7 (10.6) | 62.6 (18.4) | 1.85 (1.33–2.57) | < 0.001 |
A–T | 155.7 (11.9) | 30.6 (9.0) | 0.80 (0.53–1.21) | 0.298 |
rs1801133-rs4846052 | ||||
G–C | 814.0 (62.4) | 186.0 (54.7) | 1 | |
A–C | 399.0 (30.6) | 103.0 (30.3) | 1.13 (0.86–1.48) | 0.374 |
G–T | 91.0 (7.0) | 51.0 (15.0) | 2.45 (1.68–3.58) | < 0.001 |
rs2066470-rs3737964 | ||||
G–C | 1025.6 (78.7) | 245.0 (72.1) | 1 | |
G–T | 134.4 (10.3) | 62.0 (18.2) | 1.93 (1.39–2.69) | < 0.001 |
A–C | 138.4 (10.6) | 32.0 (9.4) | 0.97 (0.64–1.46) | 0.876 |
Interactions between different SNPs on the risk of total CHD
Interaction model | Training bal. acc | Testing bal. acc | P† | CV consistency |
---|---|---|---|---|
rs1801133 | 0.5487 | 0.5282 | 0.0547 | 9/10 |
rs2066470-rs1801131 | 0.5956 | 0.5929 | 0.0010 | 10/10 |
rs2274976-rs1801133-rs1801131 | 0.6232 | 0.5961 | 0.0010 | 5/10 |
Variable 1 | Variable2 | Variable 3 | OR (95% CI)† | P |
---|---|---|---|---|
rs2066470-rs1801131 interaction | ||||
rs2066470 | rs1801131 | |||
GG | TT | 1 | ||
GA + AA | TT | 1.69 (0.51–5.53) | 0.390 | |
GG | TG + GG | 2.16 (1.41–3.30) | 0.000 | |
GA + AA | TG + GG | 0.87 (0.59–1.29) | 0.496 | |
rs2274976-rs1801133-rs1801131 interaction | ||||
rs2274976 | rs1801133 | rs1801131 | ||
CC | GG | TT | 1 | |
CT + TT | GG | TT | – | – |
CC | GG | TG + GG | 2.08 (1.17–3.67) | 0.012 |
CT + TT | GG | TG + GG | 1.16 (0.68–2.01) | 0.584 |
CC | GA + AA | TT | 1.87 (1.24–2.82) | 0.003 |
CT + TT | GA + AA | TT | 0.91 (0.68–1.65) | 0.511 |
CC | GA + AA | TG + GG | 6.18 (2.83–13.51) | 0.000 |
CT + TT | GA + AA | TG + GG | 1.25 (0.69–2.28) | 0.464 |