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.