Background
Methods
Ethics statement
Study population
Platelet aggregation test
Genotyping
Assessment of clinical outcomes
Statistical analysis
Results
Occurrence of AR in acute IS patients
Parameter | AR + ASR | AS |
P-value |
---|---|---|---|
n = 220 |
n = 630 | ||
Age (years) | 70.8 ± 12.76 | 70.01 ± 11.35 | 0.94 |
Gender (female, %) | 122 (55.45) | 285 (45.24) | 0.02 |
Body mass index (kg/m2) | 23.85 ± 3.34 | 23.92 ± 3.32 | 0.99 |
Current smoking (n, %) | 66 (30.00) | 182 (28.89) | 0.62 |
Hypertension (n, %) | 157 (71.36) | 439 (69.68) | 0.89 |
Diabetes (n, %) | 79 (35.91) | 112 (17.78) | <0.001 |
Previous MI (n, %) | 7 (3.2) | 14 (2.2) | 0.72 |
NIHSS score at enrollment | 5.91 ± 1.81 | 5.87 ± 1.86 | 0.89 |
TC (mmol/L) | 5.32 ± 1.18 | 5.29 ± 1.76 | 0.26 |
TG (mmol/L) | 1.80 ± 0.83 | 1.79 ± 0.90 | 0.96 |
HDL-C (mmol/L) | 1.32 ± 0.32 | 1.31 ± 0.33 | 0.85 |
LDL-C (mmol/L) | 3.13 ± 0.92 | 2.93 ± 0.86 | <0.001 |
Fasting glucose (mmol/L) | 7.21 ± 2.12 | 6.43 ± 1.86 | <0.001 |
Platelet count (×109/L) | 193.01 ± 28.62 | 196.42 ± 30.46 | 0.79 |
Stroke subtype | |||
Atherothrombotic (n, %) | 135 (61.36) | 384 (60.95) | 0.86 |
Small artery disease (n, %) | 85 (38.64) | 246 (39.05) | 0.86 |
Association of SNPs with AR
AR + ASR | AS |
P-value | |
---|---|---|---|
n = 220 |
n = 630 | ||
COX-1 (rs1236913) | |||
CC | 198 (90.0) | 567 (90.0) | 0.99 |
CT + TT | 22 (10) | 63 (10.0) | |
COX-1 (rs3842787) | |||
CC | 171 (77.7) | 504 (80.0) | 0.76 |
CT + TT | 49 (22.3) | 126 (20.0) | |
COX-2 (rs689466) | |||
AA | 63 (28.6) | 180 (29.6) | 0.89 |
AG + GG | 157 (71.4) | 450 (71.4) | |
COX-2 (rs20417) | |||
GG | 142 (64.5) | 441 (70.0) | 0.26 |
GC + CC | 78 (35.5) | 189 (30.0) | |
TXAS1 (rs194149) | |||
GG | 75 (34.1) | 190 (30.2) | 0.42 |
AG + AA | 145 (65.1) | 440 (69.8) | |
TXAS1 (rs2267679) | |||
TT | 178 (80.9) | 522 (82.9) | 0.53 |
CC + CT | 42 (19.1) | 108 (17.1) | |
TXAS1 (rs41708) | |||
GG | 136 (61.8) | 373 (59.2) | 0.72 |
TT + GT | 84 (38.2) | 257 (40.8) | |
P2Y1 (rs701265) | |||
AA | 116 (52.7) | 341 (54.1) | 0.48 |
AG + GG | 104 (47.3) | 289 (45.9) | |
P2Y1 (rs1439010) | |||
AA | 114 (51.8) | 346 (54.9) | 0.32 |
AG + GG | 106 (48.2) | 284 (45.1) | |
P2Y1 (rs1371097) | |||
CC | 106 (48.2) | 373 (59.2) | 0.01 |
TT + CT | 114 (51.8) | 257 (40.8) | |
P2Y12 (rs16863323) | |||
CC | 48 (21.8) | 158 (25.1) | 0.21 |
TT + CT | 172 (78.2) | 472 (74.9) | |
P2Y12 (rs9859538) | |||
GG | 154 (70.0) | 472 (74.9) | 0.16 |
AG + AA | 66 (30.0) | 158 (25.1) | |
GPIIIa (rs2317676) | |||
AA | 132 (60.0) | 404 (64.1) | 0.24 |
AG + GG | 88 (40.0) | 64 (35.9) | |
GPIIIa (rs11871251) | |||
AA | 77 (35.0) | 190 (30.2) | 0.51 |
AG + GG | 143 (65.0) | 440 (69.8) |
Gene-gene interaction and its association with AR
rs20417 | GG | CC | CC | CC | GC | CC, GC | CC | CC, GC |
---|---|---|---|---|---|---|---|---|
rs1371097 | CC | TT | TT | CT | CT | TT | TT, CT | TT, CT |
rs2317676 | AA | GG | AG, GG | AG | AG | GG | GG | GG, AG |
OR | 1 a
| 2.72 | 1.91 | 2.28 | 1.31 | 1.08 | 1.11 | 1.05 |
95% CI | - | 1.18-6.86 | 1.07–3.84 | 1.13–5.33 | 0.98–3.26 | 0.72–1.85 | 0.62–2.21 | 0.64–1.75 |
P value | - | 0.004 | 0.034 | 0.025 | 0.087 | 0.257 | 0.452 | 0.678 |
Risk factors for ASR + AR
Risk factor |
OR
| 95% CI |
P value |
---|---|---|---|
Female | 0.86 | 0.69–1.34 | 0.232 |
Diabetes mellitus | 2.02 | 1.14–4.23 | 0.023 |
High LDL-C | 0.97 | 0.92–2.87 | 0.102 |
High blood glucose | 1.02 | 0.93–3.42 | 0.086 |
Rs1371097TT/CT | 0.92 | 0.84–2.34 | 0.124 |
High-risk interactive variable | 2.35 | 1.87–6.86 | 0.002 |
Clinical outcome
AR + ASR | AS |
P value | |
---|---|---|---|
n = 220 |
n = 630 | ||
END (n, %) | 69 (31.4) | 52 (8.3) | <0.001 |
ERIS (n, %) | 5 (2.3) | 12 (1.9) | 0.74 |
MI (n, %) | 2 (0.9) | 4 (0.6) | 0.83 |
Death (n, %) | 0 (0.0) | 2 (0.3) | 0.82 |
Factor | Hazard ratio | 95% CI |
P value |
---|---|---|---|
Age | 0.86 | 0.69–1.42 | 0.82 |
Diabetes mellitus | 1.18 | 0.97–2.85 | 0.08 |
High fasting glucose | 1.56 | 1.06–4.78 | 0.03 |
AR + ASR | 2.04 | 1.36–6.25 | 0.01 |
High-risk interactive genotypes | 2.47 | 1.42–7.84 | <0.01 |
Effect of genotypes on platelet aggregation in both pre- and post-aspirin treatment
Pre-aspirin aggregation | Platelet | Post-aspirin aggregation | Platelet | |
---|---|---|---|---|
AA- induced | ADP-induced | AA- induced | ADP-induced | |
COX-1 (rs1236913) | ||||
CC (n = 765) | 88.4 ± 15.7 | 89.2 ± 14.7 | 18.9 ± 9.2 | 66.8 ± 12.8 |
CT + TT (n = 85) | 89.2 ± 14.6 | 89.7 ± 13.2 | 19.4 ± 8.8 | 67.5 ± 10.8 |
P-value | 0.65 | 0.73 | 0.63 | 0.57 |
COX-1 (rs3842787) | ||||
CC (n = 675) | 87.9 ± 16.3 | 88.6 ± 14.7 | 19.2 ± 8.4 | 67.7 ± 11.5 |
CT + TT (n = 175) | 89.7 ± 13.6 | 90.1 ± 15.8 | 19.0 ± 7.8 | 66.6 ± 12.3 |
P-value | 0.15 | 0.21 | 0.86 | 0.28 |
COX-2 (rs689466) | ||||
AA (n = 243) | 88.9 ± 16.3 | 89.2 ± 12.8 | 20.1 ± 10.2 | 66.8 ± 13.2 |
AG + GG (n = 607) | 89.7 ± 14.1 | 90.3 ± 16.9 | 18.9 ± 9.8 | 67.2 ± 11.5 |
P-value | 0.51 | 0.36 | 0.12 | 0.67 |
COX-2 (rs20417) | ||||
GG (n = 583) | 87.9 ± 15.4 | 88.3 ± 15.2 | 18.2 ± 8.6 | 65.9 ± 13.4 |
GC + CC (n = 267) | 89.7 ± 15.7 | 89.6 ± 14.6 | 19.5 ± 9.6 | 67.1 ± 14.9 |
P-value | 0.13 | 0.26 | 0.34 | 0.07 |
TXAS1 (rs194149) | ||||
GG (n = 265) | 90.2 ± 16.7 | 89.4 ± 12.9 | 19.1 ± 7.6 | 67.9 ± 12.2 |
AG + AA (n = 585) | 88.6 ± 17.5 | 88.9 ± 15.6 | 18.7 ± 6.7 | 68.4 ± 13.8 |
P-value | 0.22 | 0.64 | 0.47 | 0.64 |
TXAS1 (rs2267679) | ||||
TT (n = 700) | 88.9 ± 17.7 | 89.1 ± 14.9 | 19.3 ± 8.9 | 66.5 ± 14.2 |
CC + CT (n = 150) | 90.3 ± 15.6 | 90.2 ± 16.4 | 18.4 ± 8.2 | 67.9 ± 15.5 |
P-value | 0.33 | 0.44 | 0.19 | 0.31 |
TXAS1 (rs41708) | ||||
GG (n = 509) | 88.8 ± 13.6 | 88.9 ± 15.2 | 18.8 ± 7.2 | 68.1 ± 12.5 |
TT + GT (n = 341) | 90.1 ± 17.8 | 89.4 ± 13.8 | 19.3 ± 8.4 | 67.6 ± 11.1 |
P-value | 0.18 | 0.63 | 0.41 | 0.54 |
P2Y1 (rs701265) | ||||
AA (n = 457) | 88.9 ± 15.3 | 88.7 ± 16.1 | 19.2 ± 7.7 | 67.8 ± 13.2 |
AG + GG (n = 393) | 89.6 ± 17.7 | 89.5 ± 14.2 | 18.4 ± 8.1 | 68.5 ± 14.4 |
P-value | 0.54 | 0.42 | 0.15 | 0.44 |
P2Y1 (rs1439010) | ||||
AA (n = 460) | 90.3 ± 16.8 | 90.1 ± 16.6 | 19.1 ± 6.8 | 66.9 ± 13.6 |
AG + GG (n = 390) | 88.5 ± 15.2 | 89.0 ± 15.3 | 18.7 ± 7.4 | 67.7 ± 12.2 |
P-value | 0.11 | 0.31 | 0.42 | 0.34 |
P2Y1 (rs1371097) | ||||
CC (n = 479) | 89.2 ± 15.6 | 87.9 ± 16.2 | 18.8 ± 7.2 | 68.1 ± 12.5 |
TT + CT (n = 371) | 88.6 ± 14.1 | 89.2 ± 15.6 | 19.3 ± 8.4 | 67.6 ± 11.1 |
P-value | 0.57 | 0.21 | 0.31 | 0.62 |
P2Y12 (rs16863323) | ||||
CC (n = 206) | 87.9 ± 16.4 | 88.8 ± 16.4 | 18.9 ± 7.6 | 67.2 ± 13.2 |
TT + CT (n = 644) | 89.9 ± 18.7 | 89.2 ± 14.5 | 18.7 ± 8.2 | 67.8 ± 12.3 |
P-value | 0.14 | 0.76 | 0.73 | 0.51 |
P2Y12 (rs9859538) | ||||
GG (n = 626) | 88.5 ± 16.5 | 88.9 ± 14.3 | 18.4 ± 8.7 | 66.7 ± 11. |
AG + AA (n = 224) | 89.9 ± 16.8 | 90.1 ± 16.7 | 19.1 ± 7.9 | 67.5 ± 13.6 |
P-value | 0.28 | 0.31 | 0.33 | 0.41 |
GPIIIa (rs2317676) | ||||
AA (n = 536) | 89.5 ± 15.2 | 87.9 ± 13.7 | 19.2 ± 8.2 | 68.3 ± 14.2 |
AG + GG (n = 314) | 88.2 ± 15.7 | 89.4 ± 17.8 | 18.5 ± 7.1 | 67.4 ± 13.3 |
P-value | 0.32 | 0.23 | 0.26 | 0.36 |
GPIIIa (rs11871251) | ||||
AA (n = 267) | 89.2 ± 12.6 | 89.8 ± 16.6 | 19.4 ± 8.7 | 66.9 ± 15.7 |
AG + GG (n = 583) | 88.6 ± 14.9 | 89.2 ± 14.3 | 18.6 ± 7.5 | 67.5 ± 14.4 |
P-value | 0.53 | 0.56 | 0.19 | 0.49 |
High-risk interactive genotypes | ||||
Yes (n = 147) | 90.6 ± 18.4 | 90.3 ± 17.5 | 30.3 ± 9.2 | 79.9 ± 12.2 |
No (n = 703) | 88.8 ± 16.7 | 88.7 ± 13.8 | 15.6 ± 6.8 | 62.3 ± 11.1 |
P-value | 0.28 | 0.27 | < 0.001 | < 0.001 |