Discussion
This study aimed to determine the influence of gene polymorphisms on clinical adversities following dual antiplatelet therapy. Notably, the polymorphisms ITGA2 C807T (rs1126643) and G873A (rs1062535) were found to have a significant association with the onset of adverse clinical events. ITGA2, located on chromosome 5q23-31, encodes the GP Ia/IIa - a crucial platelet integrin receptor - with 807T/C situated in exon 7 and 873A/G within the intron of ITGA2. The GP Ia/IIa complex (integrin α2b1) of platelet glycoprotein receptors binds to exposed collagen, facilitating stable platelet adhesion and activation [18]. These connections trigger potent signaling cascades culminating in thrombosis. Existing literature reveals that platelet surface α2b1 levels correlate with the adhesive capacity and extent of platelets to collagen in the bloodstream [19]. A deficit in GP Ia/IIa, either congenital or acquired, can precipitate hemorrhagic tendencies, with SNPs in the ITAG2 gene modulating the expression of GP Ia/IIa [20].
The C807T has two alleles, C and T, resulting in three genotypes: CC, CT, and TT. Preliminary research indicated elevated GP Ia/IIa expression in individuals possessing the T allele, suggesting its thrombogenic potential. Consequently, patients with the CC genotype could be more receptive to aspirin and clopidogrel treatment compared to those with CT or TT genotypes [21,22]. Nonetheless, previous studies investigating the genetic links between glycoprotein gene polymorphism and ischemic stroke have produced mixed findings. The T allele, in contrast to the C allele, hasn’t been linked with heightened cardiovascular event risks in patients with cardiovascular and cerebrovascular diseases undergoing aspirin and clopidogrel treatment [23,24]. The genetic polymorphism landscape of ITGA2 varies across populations. Despite expecting expression patterns of different Gplana/IIa genotypes to abide by straightforward Mendelian inheritance, the prevalent expression of the ostensibly low-risk CC/TT genotype in general European demographics implies its protective nature and potential pre-thrombotic advantage over TT/AA [25]. Beyond genetics, other clinical factors might modulate patients’ responsiveness to aspirin and clopidogrel. A meta-analysis encompassing 15 studies with 2242 cases and 2408 controls identified a correlation between the ITGA2-C807T polymorphism and ischemic stroke susceptibility, specifically in Asians and in-patients, but this was absent in Caucasians and out-patients [26]. Additionally, evidence suggests that C807T mutations might elevate plasma lipid concentrations, amplifying stroke risk [27].
The G873A (rs1062535) polymorphism in the ITGA2 gene is characterized by a G>A transition. Certain studies postulate that patients with the GG genotype might experience reduced residual platelet reactivity upon aspirin and clopidogrel treatment in contrast to those with the AG or AA genotype. In our cohort, we observed a heightened risk association for clinical outcomes with allele G over allele A. Yet, some research counters this, suggesting no significant impact of the 873A locus polymorphism on adverse cardiovascular or cerebrovascular incidents [22].
In summary, the polymorphisms ITGA2 rs1126643 and rs1062535 could heighten the vulnerability to subsequent vascular incidents in Chinese patients diagnosed with either extracranial or intracranial occlusive conditions. Although our study did not identify the effects of previously documented pharmacogenetic-related SNPs involved in antiplatelet therapy, it’s imperative to note the limited scope of our research. Hence, larger studies are essential for confirming these findings.