Abstract
Large artery atherosclerotic stroke (LAAS) is the most common ischemic stroke (IS) subtype, and microemboli may be clinically important for indicating increased risk of IS. The inflammatory process of atherosclerosis is well known, and lymphoid phosphatase (Lyp), which is encoded by the protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene, plays an important role in the inflammatory response. Our study was intended to evaluate the relationship between PTPN22 gene and LAAS and microembolic signals (MES). Three loci of the PTPN22 gene (rs2476599, rs1217414, and rs2488457) were analyzed in 364 LAAS patients and 369 control subjects. A genotyping determination was performed using the TaqMan assay. The G allele of rs2488457 might be related to a higher risk for developing LAAS and MES (odds ratio (OR) = 1.456, 95% confidence interval (CI) 1.156-1.833, P = 0.001; OR = 1.652, 95% CI 1.177-2.319, P = 0.004, respectively). In the LAAS group, the prevalence of the GTG haplotype was higher (P < 0.001) and the prevalence of the GCC haplotype was lower (P = 0.001). An interaction analysis of rs2488457 with smoking showed that smokers with the CG/GG genotypes had a higher risk of LAAS, compared to nonsmokers with the rs2488457 CC genotype (OR = 2.492, 95% CI 1.510–4.114, P < 0.001). Our research indicated that the PTPN22 rs2488457 might be related to the occurrence of LAAS and MES in the Han Chinese population. In addition, the rs2488457 polymorphism and the environmental factor of smoking jointly influenced the susceptibility of LAAS.
Highlights
Stroke is considered the most general cause of adult-acquired deformity [1]
The inclusion criteria of the cases were the presence of ischemic stroke, which was confirmed by magnetic resonance imaging (MRI) or computer tomography (CT), and the presence of cardiac and cerebral vascular lesions, which were confirmed by echocardiography, transcranial Doppler ultrasonography (TCD), brain magnetic resonance angiography (MRA), or whole-brain digital subtraction angiography (DSA)
The results demonstrated that the frequency of G allele in the protein tyrosine phosphatase nonreceptor type 22 (PTPN22) rs2488457 was higher in the large artery atherosclerotic stroke (LAAS) group, which suggested that G allele might be a potential risk marker for the prediction of LAAS
Summary
Stroke is considered the most general cause of adult-acquired deformity [1]. It is logical that ischemic stroke is a complicated and multifactorial disease that is influenced by several risk factors, including environmental and genetic factors [3]. In the age of precision medicine, much research focused on the relationship between genetic factors, such as single-nucleotide polymorphisms (SNPs), and susceptibility to IS [4]. On the basis of the TOAST (Trial of ORG 10172 in Acute Stroke Treatment) [5] classification system, the main subtype of ischemic stroke is large artery atherosclerotic stroke (LAAS) [6]. It will be of great significance to study the relationship between SNPs and LAAS for the prevention, diagnosis, treatment, and prognosis of IS [7]
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