Abstract
BackgroundThe genetic risk factors for carotid stenosis are not fully understood. The aim of this study is to investigate the relationship between variants in platelet activation-relevant genes and carotid stenosis in patients with ischemic stroke (IS).MethodsEleven variants of platelet activation-relevant genes, aggregates of platelet-leukocyte, and platelet aggregation were examined in 236 IS patients with carotid stenosis and 378 patients without carotid stenosis. High-resolution B-mode ultrasound was used to assess carotid stenosis. Generalized multifactor dimensionality reduction (GMDR) methods were applied in analyzing gene-gene interactions to determine whether there was any interactive role of assessed variants in affecting risk of carotid stenosis.ResultsPlatelet aggregation and aggregates of platelet-leukocyte showed higher value in patients with carotid stenosis, compared with patients without carotid stenosis. Excluding potential disturbance variables, these 11 variants were not associated with carotid stenosis. However, according to the GMDR analysis, gene-gene interactions among TXA2R rs1131882, P2Y1 rs1371097 and GPIIIa rs2317676 had a synergistic influence on carotid stenosis. The high-risk interactions between the three variants showed a relationship with higher platelet activation, and have independent associations with risk of carotid stenosis (OR = 2.72, 95% CI: 1.28–7.82, P = 0.001).ConclusionThe interactions among rs1131882, rs1371097 and rs2317676 perhaps increase the risk of symptomatic carotid stenosis, and maybe a potential marker for carotid stenosis. In this study, the combinatorial analysis made good use in elucidating complex risk factors in the heredity of carotid stenosis.
Highlights
The genetic risk factors for carotid stenosis are not fully understood
Compared with patients without carotid stenosis, the platelet aggregation induced by Arachidonic acid (AA) or adenosine diphosphate (ADP) and platelet-leukocyte aggregates were significantly higher in patients with carotid stenosis (Table 1)
The frequency of TXA2 receptor (TXA2R) rs1131882TT, P2Y1 rs13710 97TT, TXAS1 rs41708TT, and glycoprotein IIIa (GPIIIa) rs2317676GG was significantly higher in patients with carotid stenosis than those without carotid stenosis (Table 2)
Summary
The genetic risk factors for carotid stenosis are not fully understood. The aim of this study is to investigate the relationship between variants in platelet activation-relevant genes and carotid stenosis in patients with ischemic stroke (IS). Carotid atherosclerosis is a leading cause of stroke. Severe internal carotid artery stenosis (≥ 50%) is often accompanied by carotid atherosclerosis and emboli, thereby preventing blood flow to the brain, which increases the risk of stroke as well [2, 3]. The genetic etiology of carotid stenosis has been proposed. Variants in inflammation and endothelial functions genes have been reported to play roles in atherosclerosis pathogenesis in the Dominican population [6]. In 2016, our previous studies illustrated the variants in Cytochrome P450 genes and eicosanoid genes were independently associated with carotid stenosis [7, 8]
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