Background
Methods
Population and the definition of risk factors
Genotyping of SNPs
SNP | Gene | Position | primer |
---|---|---|---|
rs8176528 | TFPI | intron | forward: 5′- CAGTTCGTGTAGGGTTACTCAT −3’ |
reverse:5′- CCAGAGACTTTATGAGTGTCT −3’ | |||
rs10153820 | TFPI | 5′ upstream region | forward: 5′-CGTTGGAGGTCTCTCTTAGT-3’ |
reverse:5′- CTGGGCTGAGTAGCCAAGTT-3’ | |||
rs6434222 | TFPI | intron | forward: 5′-GTTTGGTTCAAGAGAGGAACT-3’ |
reverse:5′- CATGACTCAGCTGCCAGGACT-3’ | |||
rs7586970 | TFPI | Serine to Asn | forward: 5′- GAAGGCGTTCAGAAAGACTTGGT-3’ |
reverse:5′-CCCTCAGCATTGACCACAGT-3’ |
Statistical analysis
Results
Characteristics of the study population
Population 1 | Population 2 | |||||
---|---|---|---|---|---|---|
case (n = 808) | control (n = 829) |
P value | case (n = 463) | control (n = 458) |
P value | |
age (year) | 60.36 ± 10.22 | 61.12 ± 12.01 | 0.166 | 54.06 ± 8.76 | 53.27 ± 9.06 | 0.175 |
male | 634 (78.5%) | 647 (78.0%) | 0.837 | 335 (72.4%) | 332 (72.5%) | 0.963 |
BMI (kg/m2) | 25.70 ± 3.28 | 24.97 ± 3.08 | <0.001 | 25.56 ± 3.26 | 24.20 ± 2.89 | <0.001 |
smoking | 367 (45.4%) | 111 (13.4%) | <0.001 | 269 (58.1%) | 232 (50.7%) | <0.001 |
Hypertension | 528 (65.3%) | 311 (37.5%) | <0.001 | 294 (63.5%) | 118 (25.8%) | <0.001 |
diabetes mellitus | 225 (27.8%) | 104 (12.5%) | <0.001 | 125 (27.0%) | 30 (6.6%) | <0.001 |
hyperlipidemia | 439 (54.3%) | 521 (62.8%) | <0.001 | 314 (67.8%) | 181 (39.5%) | <0.001 |
Genotype distribution and genotype association analysis
Population 1 | Population 2 | ||||||
---|---|---|---|---|---|---|---|
SNP | genotype | CAD n (%) | Non-CAD n (%) | P | CAD n (%) | Non-CAD n (%) | P |
rs8176528 | 808 | 829 | 463 | 458 | |||
GG | 656 (81.2) | 694 (83.7) | 0.146 | 380 (82.1) | 384 (83.8) | 0.486 | |
AA GA | 40 (5.0) 112 (13.8) | 46 (5.6) 89 (10.7) | 18 (3.9) 65 (14.0) | 21 (4.6) 53 (11.6) | |||
Allelic A frequency (%) | 11.8 | 10.9 | 10.9 | 10.3 | |||
rs10153820 | 808 | 829 | 463 | 458 | |||
GG | 415 (51.4) | 420 (50.7) | 0.792 | 285 (61.6) | 286 (62.5) | 0.959 | |
AA GA | 48 (5.9) 345 (42.7) | 56 (6.7) 353 (42.6) | 81 (17.5) 97 (20.9) | 79 (17.2) 93 (20.3) | |||
Allelic A frequency (%) | 27.3 | 28.0 | 27.9 | 27.4 | |||
rs6434222 | 808 | 829 | 463 | 458 | |||
TT | 433 (53.6) | 496 (59.8) | <0.001 | 235 (50.7) | 285 (62.2) | <0.001 | |
AA TA | 48 (5.9) 327 (40.5) | 99 (11.9) 234 (28.3) | 11 (2.4) 217 (46.9) | 60 (13.1) 113 (24.7) | |||
Allelic A frequency (%) | 26.2 | 26.1 | 25.8 | 25.4 | |||
rs7586970 | 808 | 829 | 463 | 458 | |||
TT | 681 (84.3) | 703 (84.8) | 0.020 | 384 (82.9) | 391 (85.4) | 0.018 | |
CC TC | 36 (4.5) 91 (11.2) | 57 (6.9) 69 (8.3) | 21 (4.5) 58 (12.6) | 32 (7.0) 35 (7.6) | |||
Allelic C frequency (%) | 10.1 | 11.0 | 10.8 | 10.8 |
SNP | genotype | Population 1 | Population 2 | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
diabetes mellitus | Non- diabetes mellitus | diabetes mellitus | Non- diabetes mellitus | ||||||||||
CAD n (%) | Non-CAD n(%) |
P
| CAD n (%) | Non-CAD n (%) |
P
| CAD n (%) | Non-CAD n (%) |
P
| CAD n (%) | Non-CAD n (%) |
P
| ||
Rs8176528 | GG | 225 | 104 | 0.417 | 583 | 725 | <0.001 | 125 | 30 | 0.726 | 338 | 428 | 0.003 |
199 | 76 | 457 | 618 | 65 | 18 | 315 | 366 | ||||||
(88.4) | (73.1) | (78.4) | (85.2) | (52) | (60.0) | (93.2) | (85.5) | ||||||
AA | 9 | 5 | 31 | 41 | 9 | 2 | 9 | 19 | |||||
(4.0) | (4.8) | (5.3) | (5.7) | (7.2) | (6.7) | (2.7) | (4.4) | ||||||
GA | 17 | 23 | 95 | 66 | 51 | 10 | 14 | 43 | |||||
(7.6) | (22.1) | (16.3) | (9.1) | (40.8) | (33.3) | (4.1) | (10.1) | ||||||
Rs10153820 | GG | 225 | 104 | 0.002 | 583 | 725 | 0.063 | 125 | 30 | 0.038 | 338 | 428 | 0.392 |
103 | 67 | 312 | 353 | 86 | 15 | 199 | 271 | ||||||
(45.8) | (64.4) | (53.5) | (48.7) | (68.8) | (50.0) | (58.9) | (63.3) | ||||||
AA | 27 | 13 | 21 | 43 | 19 | 4 | 62 | 75 | |||||
(12.0) | (12.5) | (3.6) | (5.9) | (15.2) | (13.3) | (18.3) | (17.5) | ||||||
GA | 95 | 24 | 250 | 329 | 20 | 11 | 77 | 82 | |||||
(42.2) | (23.1) | (42.9) | (45.4) | (16.0) | (36.7) | (22.8) | (19.2) | ||||||
225 | 104 | 583 | 725 | 125 | 30 | 338 | 428 | ||||||
Rs6434222 | TT | 107 | 53 | 0.803 | 326 | 443 | <0.001 | 65 | 17 | 0.675 | 170 | 268 | <0.001 |
(47.6) | (51.0) | (55.9) | (61.1) | (52.0) | (56.7) | (50.3) | (62.6) | ||||||
AA | 21 | 8 | 27 | 91 | 5 | 2 | 6 | 58 | |||||
(9.3) | (7.7) | (4.6) | (12.6) | (4.0) | (6.6) | (1.8) | (13.6) | ||||||
TA | 97 | 43 | 230 | 191 | 55 | 11 | 162 | 102 | |||||
(43.1) | (41.3) | (39.5) | (26.3) | (44.0) | (36.7) | (47.9) | (23.8) | ||||||
225 | 104 | 583 | 725 | 125 | 30 | 338 | 428 | ||||||
Rs7586970 | TT | 161 | 76 | 0.926 | 520 | 627 | 0.043 | 67 | 13 | 0.065 | 317 | 378 | 0.027 |
(71.6) | (73.1) | (89.2) | (86.5) | (53.6) | (43.3) | (93.8) | (88.3) | ||||||
CC | 13 | 5 | 23 | 52 | 13 | 8 | 8 | 24 | |||||
(5.8) | (4.8) | (3.9) | (7.2) | (10.4) | (26.7) | (2.4) | (5.6) | ||||||
TC | 51 | 23 | 40 | 46 | 45 | 9 | 13 | 26 | |||||
(22.6) | (22.1) | (6.9) | (6.3) | (36.0) | (30.0) | (3.8) | (6.1) |
SNP | genotype | Population 1 | Population 2 | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
men | women | men | women | ||||||||||
CAD n (%) | Non-CAD n (%) |
P
| CAD n (%) | Non-CAD n (%) |
P
| CAD n (%) | Non-CAD n (%) |
P
| CAD n (%) | Non-CAD n (%) |
P
| ||
Rs8176528 | GG | 634 | 647 | 0.281 | 174 | 182 | 0.484 | 335 | 332 | 0.327 | 128 | 126 | 0.913 |
512 | 538 | 144 | 156 | 273 | 281 | 107 | 103 | ||||||
(80.8) | (83.2) | (82.8) | (85.7) | (81.5) | (84.7) | (83.6) | (81.7) | ||||||
AA | 33 | 37 | 7 | 9 | 13 | 15 | 5 | 6 | |||||
(5.2) | (5.7) | (4.0) | (5.0) | (3.9) | (4.5) | (3.9) | (4.8) | ||||||
GA | 89 | 72 | 23 | 17 | 49 | 36 | 16 | 17 | |||||
(14.0) | (11.1) | (13.2) | (9.3) | (14.6) | (10.8) | (12.5) | (13.5) | ||||||
Rs10153820 | GG | 634 | 647 | 0.838 | 174 | 182 | 0.343 | 335 | 332 | 0.988 | 128 | 126 | 0.782 |
306 | 319 | 109 | 101 | 204 | 201 | 81 | 85 | ||||||
(48.3) | (49.3) | (62.6) | (55.5) | (60.9) | (60.5) | (63.3) | (67.4) | ||||||
AA | 41 | 45 | 7 | 11 | 59 | 60 | 22 | 19 | |||||
(6.4) | (7.0) | (4.0) | (6.0) | (17.6) | (18.1) | (17.2) | (15.1) | ||||||
GA | 287 | 283 | 58 | 70 | 72 | 71 | 25 | 22 | |||||
(45.3) | (43.7) | (33.4) | (38.5) | (21.5) | (21.4) | (19.5) | (17.5) | ||||||
Rs6434222 | TT | 634 | 647 | <0.001 | 174 | 182 | 0.003 | 335 | 332 | <0.001 | 128 | 126 | 0.001 |
312 | 379 | 121 | 117 | 166 | 214 | 69 | 71 | ||||||
(49.2) | (58.6) | (69.5) | (64.3) | (49.6) | (64.5) | (53.9) | (56.3) | ||||||
AA | 41 | 73 | 7 | 26 | 7 | 41 | 4 | 19 | |||||
(6.5) | (11.3) | (4.1) | (14.3) | (2.0) | (12.3) | (3.1) | (15.1) | ||||||
TA | 281 | 195 | 46 | 39 | 162 | 77 | 55 | 36 | |||||
(44.3) | (30.1) | (26.4) | (21.4) | (48.4) | (23.2) | (43.0) | (28.6) | ||||||
Rs7586970 | TT | 634 | 647 | 0.068 | 174 | 182 | 0.263 | 335 | 332 | 0.056 | 128 | 126 | 0.084 |
537 | 549 | 144 | 154 | 293 | 289 | 91 | 102 | ||||||
(84.7) | (84.9) | (82.8) | (84.6) | (87.5) | (87.0) | (71.1) | (81.0) | ||||||
CC | 28 | 44 | 8 | 13 | 10 | 21 | 11 | 11 | |||||
(4.4) | (6.8) | (4.6) | (7.2) | (3.0) | (6.4) | (8.6) | (8.7) | ||||||
TC | 69 | 54 | 22 | 15 | 32 | 22 | 26 | 13 | |||||
(10.9) | (8.3) | (12.6) | (8.2) | (9.5) | (6.6) | (20.3) | (10.3) |
SNP | genotype | Population 1 | Population 2 | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
smoking | Non- smoking | smoking | Non- smoking | ||||||||||
CAD n (%) | Non-CAD n (%) |
P
| CAD n (%) | Non-CAD n (%) |
P
| CAD n (%) | Non-CAD n (%) |
P
| CAD n (%) | Non-CAD n (%) |
P
| ||
Rs8176528 | GG | 367 | 111 | 0.695 | 441 | 718 | 0.273 | 269 | 232 | 0.581 | 194 | 226 | 0.063 |
298 | 93 | 358 | 601 | 233 | 194 | 147 | 190 | ||||||
(81.2) | (83.8) | (81.2) | (83.7) | (86.6) | (83.6) | (75.8) | (84.1) | ||||||
AA | 18 | 6 | 22 | 40 | 7 | 9 | 11 | 12 | |||||
(4.9) | (5.4) | (5.0) | (5.6) | (2.6) | (3.9) | (5.7) | (5.3) | ||||||
GA | 51 | 12 | 61 | 77 | 29 | 29 | 36 | 24 | |||||
(13.9) | (10.8) | (13.8) | (10.7) | (10.8) | (12.5) | (18.5) | (10.6) | ||||||
Rs10153820 | GG | 367 | 111 | 0.998 | 441 | 718 | 0.827 | 269 | 232 | 0.871 | 194 | 226 | 0.988 |
184 | 56 | 231 | 364 | 164 | 146 | 121 | 140 | ||||||
(50.1) | (50.5) | (52.4) | (50.7) | (61.0) | (62.9) | (62.4) | (61.9) | ||||||
AA | 20 | 6 | 28 | 50 | 48 | 41 | 33 | 38 | |||||
(5.4) | (5.4) | (6.3) | (7.0) | (17.8) | (17.7) | (17.0) | (16.9) | ||||||
GA | 163 | 49 | 182 | 304 | 57 | 45 | 40 | 48 | |||||
(44.5) | (44.1) | (41.3) | (42.3) | (21.2) | (19.4) | (20.6) | (21.2) | ||||||
Rs6434222 | TT | 367 | 111 | 0.021 | 441 | 718 | <0.001 | 269 | 232 | <0.001 | 194 | 226 | <0.001 |
178 | 64 | 255 | 432 | 136 | 132 | 99 | 153 | ||||||
(48.5) | (57.7) | (57.8) | (60.2) | (50.6) | (56.9) | (51.0) | (67.7) | ||||||
AA | 20 | 11 | 28 | 88 | 7 | 39 | 4 | 21 | |||||
(5.4) | (9.9) | (6.3) | (12.3) | (2.6) | (16.8) | (2.1) | (9.3) | ||||||
TA | 169 | 36 | 158 | 198 | 126 | 61 | 91 | 52 | |||||
(46.1) | (32.4) | (35.9) | (27.5) | (46.8) | (26.3) | (46.9) | (23.0) | ||||||
Rs7586970 | TT | 367 | 111 | 0.749 | 441 | 718 | 0.064 | 269 | 232 | 0.081 | 194 | 226 | 0.202 |
306 | 92 | 375 | 611 | 221 | 194 | 163 | 197 | ||||||
(83.4) | (82.9) | (85.0) | (85.1) | (82.2) | (83.7) | (84.0) | (87.2) | ||||||
CC | 17 | 7 | 19 | 50 | 12 | 18 | 9 | 14 | |||||
(4.6) | (6.3) | (4.3) | (7.0) | (4.4) | (7.7) | (4.6) | (6.2) | ||||||
TC | 44 | 12 | 47 | 57 | 36 | 20 | 22 | 15 | |||||
(12.0) | (10.8) | (10.7) | (7.9) | (13.4) | (8.6) | (11.4) | (6.6) |
SNP | genotype | Population 1 | Population 2 | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
hypertension | Non-hypertension | hypertension | Non-hypertension | ||||||||||
CAD n (%) | Non-CAD n (%) |
P
| CAD n (%) | Non-CAD n (%) |
P
| CAD n (%) | Non-CAD n (%) |
P
| CAD n (%) | Non-CAD n (%) |
P
| ||
Rs8176528 | GG | 528 | 311 | 0.074 | 280 | 518 | 0.403 | 294 | 118 | 0.477 | 169 | 340 | 0.707 |
428 | 271 | 228 | 423 | 238 | 100 | 142 | 284 | ||||||
(81.1) | (87.1) | (81.4) | (81.7) | (81.0) | (84.7) | (84.0) | (83.5) | ||||||
AA | 26 | 10 | 14 | 36 | 13 | 6 | 5 | 15 | |||||
(4.9) | (3.2) | (5.0) | (6.9) | (4.4) | (5.1) | (3.0) | (4.4) | ||||||
GA | 74 | 30 | 38 | 59 | 43 | 12 | 22 | 41 | |||||
(14.0) | (9.7) | (13.6) | (11.4) | (14.6) | (10.2) | (13.0) | (12.1) | ||||||
Rs10153820 | GG | 528 | 311 | 0.327 | 280 | 518 | 0.381 | 294 | 118 | 0.744 | 169 | 340 | 0.797 |
268 | 174 | 147 | 246 | 175 | 75 | 110 | 211 | ||||||
(50.8) | (55.9) | (52.5) | (47.5) | (59.5) | (63.6) | (65.1) | (62.1) | ||||||
AA | 31 | 18 | 17 | 38 | 54 | 19 | 27 | 60 | |||||
(5.8) | (5.8) | (6.1) | (7.3) | (18.4) | (16.1) | (16.0) | (17.6) | ||||||
GA | 229 | 119 | 116 | 234 | 65 | 24 | 32 | 69 | |||||
(43.4) | (38.3) | (41.4) | (45.2) | (22.1) | (20.3) | (18.9) | (20.3) | ||||||
Rs6434222 | TT | 528 | 311 | <0.001 | 280 | 518 | 0.002 | 294 | 118 | <0.001 | 169 | 340 | <0.001 |
274 | 194 | 159 | 302 | 146 | 60 | 89 | 225 | ||||||
(51.9) | (62.4) | (56.8) | (58.3) | (49.7) | (50.8) | (52.7) | (66.2) | ||||||
AA | 33 | 37 | 15 | 62 | 8 (2.7) | 21 | 3 | 39 | |||||
(6.3) | (11.9) | (5.4) | (12.0) | (17.8) | (1.8) | (11.5) | |||||||
TA | 221 | 80 | 106 | 154 | 140 | 37 | 77 | 76 | |||||
(41.8) | (25.7) | (37.8) | (29.7) | (47.6) | (31.4) | (45.5) | (22.3) | ||||||
Rs7586970 | TT | 528 | 311 | 0.250 | 280 | 518 | 0.078 | 294 | 118 | 0.312 | 169 | 340 | 0.158 |
448 | 262 | 233 | 441 | 241 | 98 | 143 | 293 | ||||||
(84.8) | (84.2) | (83.3) | (85.2) | (82.0) | (83.1) | (84.6) | (86.2) | ||||||
CC | 23 | 21 | 13 | 36 | 14 | 9 | 7 | 23 | |||||
(4.4) | (6.8) | (4.6) | (6.9) | (4.8) | (7.6) | (4.1) | (6.8) | ||||||
TC | 57 | 28 | 34 | 41 | 39 | 11 | 19 | 24 | |||||
(10.8) | (9.0) | (12.1) | (7.9) | (13.2) | (9.3) | (11.3) | (7.0) |
SNP | genotype | Population 1 | Population 2 | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
hyperlipidemia | Non- hyperlipidemia | hyperlipidemia | Non- hyperlipidemia | ||||||||||
CAD n (%) | Non-CAD n (%) |
P
| CAD n (%) | Non-CAD n (%) |
P
| CAD n (%) | Non-CAD n (%) |
P
| CAD n (%) | Non-CAD n (%) |
P
| ||
Rs8176528 | GG | 439 | 521 | 0.074 | 369 | 308 | 0.651 | 314 | 181 | 0.580 | 149 | 277 | 0.166 |
356 | 447 | 300 | 247 | 269 | 157 | 111 | 227 | ||||||
(81.1) | (85.8) | (81.3) | (80.2) | (85.7) | (86.7) | (74.5) | (81.9) | ||||||
AA | 21 | 25 | 19 | 21 | 10 | 8 | 8 | 13 | |||||
(4.8) | (4.8) | (5.1) | (6.8) | (3.2) | (4.4) | (5.4) | (4.7) | ||||||
GA | 62 | 49 | 50 | 40 | 35 | 16 | 30 | 37 | |||||
(14.1) | (9.4) | (13.6) | (13.0) | (11.1) | (8.9) | (20.1) | (13.4) | ||||||
Rs10153820 | GG | 439 | 521 | 0.301 | 369 | 308 | 0.848 | 314 | 181 | 0.788 | 149 | 277 | 0.688 |
217 | 251 | 198 | 169 | 196 | 110 | 89 | 176 | ||||||
(49.4) | (48.2) | (53.7) | (54.9) | (62.4) | (60.8) | (59.7) | (63.5) | ||||||
AA | 20 | 36 | 28 | 20 | 53 | 35 | 28 | 44 | |||||
(4.6) | (6.9) | (7.6) | (6.5) | (16.9) | (19.3) | (18.8) | (15.9) | ||||||
GA | 202 | 234 | 143 | 119 | 65 | 36 | 32 | 57 | |||||
(46.0) | (44.9) | (38.7) | (38.6) | (20.7) | (19.9) | (21.5) | (20.6) | ||||||
439 | 521 | 369 | 308 | 314 | 181 | 149 | 277 | ||||||
Rs6434222 | TT | 252 | 321 | 0.002 | 181 | 175 | <0.001 | 158 | 125 | <0.001 | 77 | 160 | <0.001 |
(57.4) | (61.6) | (49.1) | (56.8) | (50.3) | (69.1) | (51.7) | (57.8) | ||||||
AA | 28 | 58 | 20 | 41 | 6 | 19 | 5 | 41 | |||||
(6.4) | (11.1) | (5.4) | (13.3) | (1.9) | (10.5) | (3.4) | (14.8) | ||||||
TA | 159 | 142 | 168 | 92 | 150 | 37 | 67 | 76 | |||||
(36.2) | (27.3) | (45.5) | (29.9) | (47.8) | (20.4) | (44.9) | (27.4) | ||||||
Rs7586970 | TT | 439 | 521 | 0.117 | 369 | 308 | 0.125 | 314 | 181 | 0.064 | 149 | 277 | 0.073 |
372 | 449 | 309 | 254 | 252 | 160 | 132 | 231 | ||||||
(84.7) | (86.2) | (83.7) | (82.5) | (80.3) | (88.4) | (88.6) | (83.4) | ||||||
CC | 19 | 32 | 17 | 25 | 16 | 6 | 5 | 26 | |||||
(4.3) | (6.1) | (4.6) | (8.1) | (5.1) | (3.3) | (3.4) | (9.4) | ||||||
TC | 48 | 40 | 43 | 29 | 46 | 15 | 12 | 20 | |||||
(11.0) | (7.7) | (11.7) | (9.4) | (14.6) | (8.3) | (8.0) | (7.2) |