3.1 Patient Characteristics
A total of 143 patients who underwent PCI with dual antiplatelet therapy were included in this study. The baseline characteristics of included patients at the first PCI are shown in Table 1.
3.2 Patient Outcome
After the first PCI, the incidence of repeat revascularization at 18, 30, and 42 months was 14.1% (20/142), 17.5% (24/137), and 39.7% (31/78), respectively.
3.3 Association of SNPs with Platelet function
3.3.1 The SNPs of candidate gene variations
To analyze the association of SNPs of candidate gene and platelet function, 372 SNPs of 4 genes (15 SNPs of NOS3, 9 SNPS of MMP3, 46 SNPs of AGT, and 302 SNPs of AGT1R) were evaluated in the current study. After adjusting for smoking status, 4 and 7 SNPs were significantly related with PRU values and ADP aggregation rate, respectively (Table 2).
3.3.2 The SNPs of pathway gene variations
To analyze the association of SNPs of pathways and PRU or ADP aggregation rate, a total of 380 genes in four pathways (platelet activation pathway, platelet amyloid precursor protein pathway, aspirin blocks signaling pathway involved in platelet activation, and clopidogrel related gene) were analyzed in our study. After adjustment of smoking status, 363 SNPs were significantly related to PRU values, and 529 SNPs were significantly related to ADP aggregation rate (Appendix Table 3). Furthermore, 25 SNPs were associated with PRU value and ADP aggregation rate; details are listed in Table 3. Among these SNPs, the P-link values of kgp10633449 were less than 0.01 both for PRU and ADP aggregation rate, and the P-link values of PRU and ADP aggregation rate were 0.00606 and 0.003235, respectively.
3.4 Association of SNPs with the outcome
3.4.1 The SNPs of candidate gene variations
To analyze the association of SNPs of candidate genes and clinical outcomes, 372 SNPs of the four genes were analyzed. After adjusting for smoking status, 10, 20, and 8 SNPs were significantly related with repeat revascularization at 18, 30, and 42 months, respectively. Meanwhile, 24, 35, and 8 SNPs were significantly related with ISR at 18, 30, and 42 months, respectively (Table 4).
3.4.2 The SNPs of pathway gene variations
In addition to platelet function, 380 identical genes were used to analyze the association between SNPs and clinical outcomes. After adjusting for smoking status, 462 SNPs were significantly related with repeat revascularization within 18 months, 500 SNPs were significantly related with it within 30 months, 273 SNPs were significantly related with it within 42 months, 468 SNPs were significantly related with ISR within 18 months, 428 SNPs were significantly related with ISR within 30 months, and 363 SNPs were significantly related with ISR within 42 months. The details of the 2494 SNPs are shown in Appendix Table 3. There were 61 SNPs and 2 SNPs significantly associated with repeat revascularization and ISR within 18 months, 30 months, and 42 months (Table 5). There were three linkage SNPs (rs3788367, kgp3029439, and kgp15051272) of CABIN1. The correlation P-link values between them and repeat revascularization at 18 months, 30 months and 42 months were 0.002694, 0.0001099 and 0.007271, respectively (P < 0.01 for all).
3.5 Association of SNPs with Platelet function and outcomes
3.5.1 The SNPs of candidate gene variations
There were two SNPs associated with both platelet function, and clinical outcome. rs 78830 of NOS3 was associated with both ADP aggregation rate (Plink-P, 0.013) and 18- month ISR (Plink-P, 0.035) and 30-month ISR (Plink-P, 0.025), respectively. rs 62275847 of AGTR1 was associated with both ADP aggregation rate (Plink-P, 0.029) and 30-month ISR (Plink-P, 0.036).
3.5.2 The SNPs of pathway gene variations
Among the 588 SNPs associated with PRU, 21, 28, and 12 were associated with ISR at 18, 30, and 42 months, and 36, 33, and 16 SNPs were associated with re-revascularization at 18, 30, and 42 months, respectively. Of the 529 SNPs associated with ADP aggregation, 13, 15, and 8 SNPs were associated with ISR at 18, 30, and 42 months, and 16, 12, and 11 SNPs were associated with repeat revascularization at 18, 30, and 42 months, respectively (Table S5).
There were four SNPs of pathway gene variations associated with both platelet function and clinical outcome. The linkage rs471683 and rs7785386 of GNAI1|GNAT3 were associated with both PRU (Plink-P, 0.016), ADP aggregation rate (Plink-P, 0.002), 18-months ISR (Plink-P, 0.013), 30-months ISR (0.035), and repeat revascularization within 30 months (Plink-P, 0.030). Rs1715389 of GNAI1|GNAT3 were associated with both PRU (Plink-P, 0.019), ADP aggregation rate (Plink-P, 0.002), 18-months ISR (Plink-P, 0.016), 30-months ISR (0.046), and repeat revascularization within 30 months (Plink-P, 0.040). Rs7313458 of ITPR2 were associated with both PRU (Plink-P, 0.024), ADP aggregation rate (Plink-P, 0.036), 18-months ISR (0.043), 30-months ISR (Plink-P, 0.004), and repeat revascularization within 18 months (Plink-P, 0.009).