Patel S. et al (2019)2323 Patel S, Arya V, Saraf A, Bhargava M, Agrawal CS. Aspirin and Clopidogrel Resistance in Indian Patients with Ischemic Stroke and its Associations with Gene Polymorphisms: A Pilot Study. Ann Indian Acad Neurol 2019;22(02):147-152
|
Case-control |
India |
Ischemic stroke |
65 |
2 |
62 |
CYP2C19 |
G |
A |
rs4244285 (CYP2C19*2) |
0.171 |
NI |
NI |
Platelet Aggregation Measurement - LTA |
75mg |
ITGA2B/ITGB3 |
T |
C |
rs5918 (PLA1/A2) |
0.960 |
NI |
NI |
Yeo et al. (2018)3535 Yeo KK, Armstrong EJ, López JE, et al. Aspirin and clopidogrel high ontreatment platelet reactivity and genetic predictors in peripheral arterial disease. Catheter Cardiovasc Interv 2018;91(07):1308-1317
|
Cohort |
USA |
Peripheral artery disease |
154 |
31 |
123 |
PTGS1 |
A |
G |
rs10306114 (A842G) |
NI |
NI |
NI |
Platelet Aggregation Measurement - VerifyNow Assay |
300mg |
PTGS1 |
C |
T |
rs3842787 (C22T) |
NI |
NI |
NI |
PTGS1 |
C |
A |
rs5788 (C644A) |
NI |
NI |
NI |
PTGS1 |
C |
A |
rs5789 (C714A) |
NI |
NI |
NI |
ITGA2 |
C |
T |
rs1126643 (C807T) |
NI |
NI |
NI |
ITGA2 |
G |
A |
rs1062535 (873G/A) |
NI |
NI |
NI |
ITGA2 |
C |
T |
rs1126643 (C807T) |
NI |
NI |
NI |
ITGB3 |
T |
C |
rs5918 (PLA1/A2) |
NI |
NI |
NI |
GP6 |
C |
T |
rs1613662 (C13254T) |
NI |
NI |
NI |
P2RY12 |
C |
T |
rs1065776 (893C > T) |
NI |
NI |
NI |
F13A1 |
G |
T |
rs5985 (V34L) |
NI |
NI |
NI |
PON1 |
A |
G |
rs662 (A576G) |
0.005 |
NI |
NI |
Wang et al. (2017)2828 Wang H, Sun X, Dong W, et al. Association of GPIa and COX-2 gene polymorphism with aspirin resistance. J Clin Lab Anal 2018;32 (04):e22331
|
Case-control |
China |
Ischemic stroke |
97 |
43 |
54 |
ITGA2 |
C |
T |
rs1126643 (C807T) |
0.210 |
NI |
NI |
Platelet Aggregation Measurement - PL-11 platelet analyzer |
100mg |
PTGS2 |
G |
C |
rs20417 (G765C) |
0.69 |
NI |
NI |
Strisciuglio et al. (2017)3636 Strisciuglio T, Barbato E, De Biase C, et al. T2238C Atrial Natriuretic Peptide Gene Variant and the Response to Antiplatelet Therapy in Stable Ischemic Heart Disease Patients. J Cardiovasc Transl Res 2018;11(01):36-41
|
Case-control |
Belgium |
Stable CAD patients undergoing elective PCI |
597 |
NI |
NI |
NPPA |
T |
C |
rs5065 (T2238C) |
0.7 |
NI |
NI |
Platelet Aggregation Measurement - VerifyNow P2Y12 |
500mg |
Yi et al. (2017)1919 Yi X, Wang C, Zhou Q, Lin J. Interaction among COX-2, P2Y1 and GPIIIa gene variants is associated with aspirin resistance and early neurological deterioration in Chinese stroke patients. BMC Neurol 2017;17(01):4
|
Case-control |
China |
Ischemic stroke |
850 |
175 |
630 |
PTGS1 |
C |
T |
rs1236913 |
0.99** |
NI |
NI |
Platelet Aggregation Measurement - LTA |
200mg (14 days) and follow-up with 100mg |
PTGS1 |
C |
T |
rs3842787 |
0.76** |
NI |
NI |
PTGS2 |
A |
G |
rs689466 |
0.89** |
NI |
NI |
PTGS2 |
G |
C |
rs20417 |
0.26** |
NI |
NI |
TXAS1 |
G |
A |
rs194149 |
0.42** |
NI |
NI |
TXAS1 |
T |
C |
rs2267679 |
0.53** |
NI |
NI |
TXAS1 |
G |
T |
rs41708 |
0.72** |
NI |
NI |
P2RY1 |
A |
G |
rs701265 |
0.48** |
NI |
NI |
P2RY1 |
A |
G |
rs1439010 |
0.32** |
NI |
NI |
P2RY1 |
C |
T |
rs1371097 |
0.01** |
NI |
NI |
P2RY12 |
C |
T |
rs16863323 |
0.21** |
NI |
NI |
P2RY12 |
G |
A |
rs9859538 |
0.16** |
NI |
NI |
ITGB3 |
A |
G |
rs2317676 |
0.24** |
NI |
NI |
ITGB3 |
A |
G |
rs11871251 |
0.51** |
NI |
NI |
Peng et al. (2016)2020 Peng LL, Zhao YQ, Zhou ZY, et al. Associations of MDR1, TBXA2R, PLA2G7, and PEAR1 genetic polymorphisms with the platelet activity in Chinese ischemic stroke patients receiving aspirin therapy. Acta Pharmacol Sin 2016;37(11):1442-1448
|
Case-control |
China |
Ischemic stroke |
283 |
250 |
33 |
ABCB1 |
C |
T |
rs1045642 |
0.021 |
0.421 |
0.233-0.759 |
Platelet Aggregation Measurement - TXB2 ELISA kit |
100mg |
TBXA2R |
G |
A |
rs1131882 |
0.028 |
2.712 |
1.080-6.810 |
PLA2G7 |
A |
G |
rs1051931 |
0.023 |
8.233 |
1.590-42.638 |
PLA2G7 |
C |
A |
rs7756935 |
0.023 |
8.233 |
1.590-42.638 |
PEAR1 |
G |
T |
rs12566888 |
0.378 |
0.660 |
0.260-1.671 |
PEAR1 |
G |
A |
rs12566888 |
0.378 |
0.660 |
0.260-1.671 |
Yi et al. (2016)88 Yi X, Cheng W, Lin J, Zhou Q, Wang C. Interaction between COX-1 and COX-2 Variants Associated with Aspirin Resistance in Chinese Stroke Patients. J Stroke Cerebrovasc Dis 2016;25(09): 2136-2144
|
Case-control |
China |
Ischemic stroke |
850 |
175 |
630 |
PTGS1 |
T |
C |
rs1236913 |
0.95** |
NI |
NI |
Platelet Aggregation Measurement- LTA |
200mg (14 days) and follow-up with 100mg |
PTGS1 |
C |
T |
rs3842787 |
0.78** |
NI |
NI |
PTGS2 |
T |
C |
rs689466 |
0.82** |
NI |
NI |
PTGS2 |
G |
C |
rs20417 |
0.42** |
NI |
NI |
Derle et al. (2016)33 Derle E, Öcal R, Kibaroğlu S, et al. Aspirin resistance in cerebro-vascular disease and the role of glycoprotein IIIa polymorphism in Turkish stroke patients. Blood Coagul Fibrinolysis 2016;27(02): 169-175
|
Case-control |
Turkey |
Acute vascular event |
208 |
67 |
141 |
ITGB3 |
T |
C |
rs5918 (PLA1/A2) |
0.277 |
NI |
NI |
Platelet Aggregation Measurement - PFA-100 system |
100-300mg |
Wang et al. (2014)2424 Wang BY, Tan SJ. Platelet glycoprotein IIIa gene polymorphism (Leu33Pro) and aspirin resistance in a very elderly Chinese population. Genet Test Mol Biomarkers 2014;18(06): 389-393
|
Case-control |
China |
> 80 years old |
450 |
236 |
214 |
ITGB3 |
T |
C |
rs5918 (PLA1/A2) |
0.002 |
NI |
NI |
Platelet Aggregation Measurement - LTA |
100mg |
Al-Azzam et al. (2013)2727 Al-Azzam SI, Alzoubi KH, Khabour OF, Tawalbeh D, Al-Azzeh O. The contribution of platelet glycoproteins (GPIa C807T and GPIba C-5T) and cyclooxygenase 2 (COX-2G-765C) polymorphisms to platelet response in patients treated with aspirin. Gene 2013;526 (02):118-121
|
Case-control |
Jordan |
Adults |
584 |
92 |
492 |
ITGA2 |
C |
T |
rs1126643 (C807T) |
0.116 |
NI |
NI |
Platelet Aggregation Measurement - Multiplate Analyzer system |
100mg |
GP1BA |
T |
C |
rs2243093 |
0.003 |
NI |
NI |
PTGS2 |
G |
C |
rs20417 |
0.485 |
NI |
NI |
Li et al. (2012)2929 Li XL, Cao J, Fan L, et al. Genetic polymorphisms of HO-1 and COX- 1 are associated with aspirin resistance defined by light transmittance aggregation in Chinese Han patients. Clin Appl Thromb Hemost 2013;19(05):513-521
|
Case-control |
China |
CAD, stroke, and peripheral artery disease |
431 |
36 |
231 |
PTGS1 |
C |
T |
rs1888943 |
0.92 |
NI |
NI |
Platelet Aggregation Measurement - LTA |
75-160mg |
PTGS1 |
A |
G |
rs1330344 |
0.1 |
NI |
NI |
PTGS1 |
C |
T |
rs3842787 |
0.92 |
NI |
NI |
PTGS1 |
G |
A |
rs5787 |
0.92 |
NI |
NI |
PTGS1 |
C |
A |
rs5789 |
1 |
NI |
NI |
PTGS1 |
G |
A |
rs5794 |
1 |
NI |
NI |
PTGS2 |
G |
C |
rs20417 |
1 |
NI |
NI |
PTGS2 |
C |
G |
rs5277 |
0.24 |
NI |
NI |
HO1 |
A |
T |
rs2071746 |
0.04 |
NI |
NI |
Wang et al. (2013)2121 Wang Z, Gao F, Men J, Yang J, Modi P, Wei M. Polymorphisms and high on-aspirin platelet reactivity after off-pump coronary artery bypass grafting. Scand Cardiovasc J 2013;47(04):194-199
|
Case-control |
China |
Patientsunderwent primary OPCAB |
210 |
62 |
148 |
TBXA2R |
T |
C |
rs4523 (T924C) |
0.001 |
4.479 |
1.811-11.077 |
Platelet Aggregation Measurement - LTA |
100mg |
ITGB3 |
T |
C |
rs5918 (PLA1/A2) |
NI |
NI |
NI |
P2RY1 |
A |
G |
rs701265 (A1622G) |
0.724 |
1.178 |
0.473-2.934 |
GP1BA |
C |
T |
rs6065 (C1018T) |
NI |
NI |
NI |
Sharma et al. (2013)3232 Sharma V, Kaul S, Al-Hazzani A, Alshatwi AA, Jyothy A, Munshi A. Association of COX-2 rs20417 with aspirin resistance. J Thromb Thrombolysis 2013;35(01):95-99
|
Case-control |
India |
Ischemic stroke |
450 |
217 |
233 |
PTGS2 |
G |
C |
rs20417 (-765G/C) |
CC: p= 0.016 GC:p= 0.02 |
CC:OR-3.157 GC: OR-1.745 |
CC: 1.241-8.033GC: 1.059-2.875 |
Clinical outcome |
75-325mg |
Sharma et al. (2013)1717 Sharma V, Dadheech S, Kaul S, Jyothy A, Munshi A. Association of ALOX5AP1 SG13S114T/A variant with ischemic stroke, stroke subtypes and aspirin resistance. J Neurol Sci 2013;331(1-2):108-113
|
Case-control |
India |
Ischemic stroke |
610 |
307 |
303 |
ALOX5AP |
T |
A |
rs9315042 (SG13S114T/A) |
<0.001 |
2.983 |
1.884-4.723 |
Clinical outcome |
75-325mg |
Fan et al. (2012) |
Case-control |
China |
CAD, hypertension, peripheral artery disease and stroke |
431 |
38 |
393 |
PTGS1 |
A |
G |
rs1330344 |
0.01 |
1.82 |
1.13-2.92 |
Platelet Aggregation Measurement - LTA and TEG Platelet Mapping Assay |
75-100 mg |
PTGS1 |
C |
T |
rs1888943 |
0.59 |
NI |
NI |
PTGS1 |
C |
T |
rs3842787 |
0.66 |
NI |
NI |
PTGS1 |
G |
A |
rs5787 |
0.49 |
NI |
NI |
PTGS1 |
C |
A |
rs5789 |
1 |
NI |
NI |
PTGS1 |
G |
A |
rs5794 |
1 |
NI |
NI |
Sharma et al. (2012)3333 Sharma V, Kaul S, Al-Hazzani A, et al. Association of C3435T multi drug resistance gene-1 polymorphism with aspirin resistance in ischemic stroke and its subtypes. J Neurol Sci 2012;315(1-2):72-76
|
Case-control |
India |
Ischemic stroke |
560 |
338 |
222 |
ABCB1 |
C |
T |
rs1045642 |
0.012 |
1.85 |
1.142-3.017 |
Clinical outcome |
75-325 mg/dia |
Gao et al. (2011)2222 Gao F, Wang ZX, Men JL, Ren J, Wei MX. Effect of polymorphism and type II diabetes on aspirin resistance in patients with unstable coronary artery disease. Chin Med J (Engl) 2011;124(11): 1731-1734
|
Case-control |
China |
Patients underwent primary OPCAB |
262 |
23 |
239 |
GP1BA |
C |
T |
rs6065 (C1018T) |
1 |
NI |
NI |
Platelet Aggregation Measurement - LTA |
100mg |
ITGB3 |
T |
C |
rs5918 (P1A1/A2) |
1 |
NI |
NI |
P2RY1 |
A |
G |
rs701265 (A1622G) |
0.991 |
NI |
NI |
TBXA2R |
T |
C |
rs4523 (T924C) |
0.01 |
NI |
NI |
Chakroun et al. (2011)3131 Chakroun T, Addad F, Yacoub S, et al. The cyclooxygenase-1 C50T polymorphism is not associated with aspirin responsiveness status in stable coronary artery disease in Tunisian patients. Genet Test Mol Biomarkers 2011;15(7-8):513-516
|
Case-control |
Tunisia |
Stable CAD |
125 |
NI |
NI |
PTGS1 |
C |
T |
rs3842787 (C50T) |
Urinary TxB2: 0.1PFA-100: 0.43 |
NI |
NI |
Platelet Aggregation Measurement - PFA-100 system and Urinary 11-dehydro-TXB2 |
250mg |
Voora et al. (2011)2626 Voora D, Horton J, Shah SH, Shaw LK, Newby LK. Polymorphisms associated with in vitro aspirin resistance are not associated with clinical outcomes in patients with coronary artery disease who report regular aspirin use. Am Heart J 2011;162(01):166-72.e1
|
Case-control |
USA |
Coronary stenosis ≥ 75% |
3449 |
865 |
2584 |
GNB3 |
C |
T |
rs5443 (C825T) |
> 0.05 |
Black: 1.15 White: 0.93 |
Black: 0.71-1.87 White: 0.82-1.07 |
Clinical Outcome |
Two groups: < 81mg and > 81mg |
ITGA2 |
C |
T |
rs1126643 (C807T) |
Black: 1.10 White: 0.99 |
Black: 0.82-1.46 White: 0.87-1.14 |
ITGB3 |
T |
C |
rs5918 |
Black: 1.03 White: 0.98 |
Black: 0.71-1.50 White: 0.85-1.13 |
GP6 |
A |
G |
rs1613662 |
Black: 0.89 White: 0.99 |
Black: 0.66-1.20 White: 0.86-1.15 |
GP1BA |
T |
C |
rs2243093 |
Black: 0.84 White: 1.01 |
Black: 0.62-1.14 White: 0.86-1.18 |
PEAR1 |
A |
C |
rs2768759 |
Black: 1.05 White: 0.95 |
Black: 0.46-2.41 White: 0.83-1.09 |
VAV3 |
A |
C |
rs6583047 |
Black: 1.06 White: 1.02 |
Black: 0.80-1.42 White: 0.89-1.16 |
F2R |
A |
T |
rs168753 |
Black: 0.96 White: 1.06 |
Black: 0.60-1.54 White: 0.91-1.23 |
THBS1 |
A |
G |
rs2228262 |
Black: 0.68 White: 1.03 |
Black: 0.34-1.36 White: 0.88-1.21 |
PTGS1 |
C |
T |
rs3842787 |
Black: 1.29 White: 1.06 |
Black: 0.94-1.77 White: 0.88-1.29 |
ADRA2A |
G |
C |
rs1800544 |
Black: 0.98 White: 0.97 |
Black: 0.63-1.51 White: 0.85-1.10 |
Pamukcu et al. (2010)2525 Pamukcu B, Oflaz H, Onur I, Hancer V, Yavuz S, Nisanci Y. Impact of genetic polymorphisms on platelet function and aspirin resistance. Blood Coagul Fibrinolysis 2010;21(01):53-56
|
Case-control |
Turkey |
Stable CAD |
126 |
30 |
96 |
F5 |
G |
A |
rs6025 (G1691A) |
0.302 |
NI |
NI |
Platelet Aggregation Measurement - PFA-100 system |
NI (The p-value for the difference between the resistant and sensitive groups was 0.681) |
F5 |
A |
G |
rs1800595 (A4070G - H1299R) |
0.191 |
F2 |
G |
A |
rs1799963 (G20210A) |
0.644 |
F13A1 |
G |
T |
rs5985 (V34L) |
0.480 |
FGB |
G |
A |
rs1800790 (G455A) |
0.814 |
SERPINE1 |
A |
G |
rs1799889 (4G/5G) |
0.656 |
ITGB3 |
T |
C |
rs5918 (HPA1a/b) |
0.623 |
MTHFR |
C |
T |
rs1801133 (C677T) |
0.362 |
MTHFR |
A |
C |
rs1801131 (A1298C) |
0.421 |
ACE |
Ins |
Del |
rs1799752 (ACE I/D) |
0.713 |
APOB |
G |
A |
rs5742904 (R3500Q) |
1 |
APOE |
T |
C |
rs429358 (C112R) |
0.695 |
APOE |
T |
C |
rs429358 (C158A) |
0.695 |
Carroll et al. (2010)3434 Carroll RC, Worthington RE, Craft RM, et al. Post interventional cardiology urinary thromboxane correlates with PlateletMapping detected aspirin resistance. Thromb Res 2010;125(04): e118-e122
|
Case-control |
USA |
Candidates for interventional cardiology on aspirin therapy |
81 |
27 |
54 |
ALOX12 |
A |
G |
rs434473 |
0.043 |
NI |
NI |
Platelet Aggregation Measurement - TEG Platelet mapping |
Not uniform |
ALOX15B |
G |
A |
rs4792147 |
0.440 |
ALOX12 |
G |
A |
rs1126667 |
0.580 |
ALOX15 |
G |
A |
rs3892408 |
NI |