Associations between thromboxane A synthase 1 gene polymorphisms and the risk of ischemic stroke in a Chinese Han population

Thromboxane A synthase 1 （TBXAS1） catalyses the synthesis of thromboxane A2 （TXA2）, which plays an important role in the pathogenesis of ischemic stroke. Thus, the TBXAS1 gene was investigated as a candidate gene involved in the formation of atherosclerosis. This case-control study collected peripheral blood specimens and clinical data of 370 ischemic stroke patients and 340 healthy controls in the Northern Chinese Han population from October 2010 to May 2011. Two TBXAS1 single-nucleotide polymorphisms, rs2267682 and rs10487667, were analyzed using a SNaPshot Multiplex sequencing assay to explore the relationships between the single-nucleotide polymorphisms in TBXAS1 and ischemic stroke. The TT genotype frequency and T allele frequency of rs2267682 in the patients with ischemic stroke were significantly higher than those in the controls （P 〈 0.01 and P = 0.02）. Furthermore, compared with the GG ＋ GT genotype, the TT rs2267682 genotype was associated with increased risk of ischemic stroke （odds ratio （OR） = 1.80, 95% confidence interval （CI）： 1.16–2.79, P 〈 0.01）. Multivariate logistic analysis with adjustments for confounding factors revealed that rs2267682 was still associated with ischemic stroke （OR = 1.94,95% CI ： 1.13–3.33, P = 0.02）. The frequency of the T-G haplotype in the patients was significantly higher than that in the controls according haplotype analysis （OR = 1.49, 95% CI： 1.10–2.00, P 〈 0.01）. These data reveal that the rs2267682 TBXAS1 polymorphism is associated with ischemic stroke. The TT genotype of TBXAS1 and T allele of rs2267682 increase susceptibility to ischemic stroke in this Northern Chinese Han population. The protocol has been registered with the Chinese Clinical Trial Registry （registration number： ChiCTR-COC-17013559）.

Serum uric acid is a risk factor for large-artery atherosclerosis cerebral infarction

Using the Trial of Org 10172 in Acute Stroke Treatment （TOAST） classification for acute ischemic stroke, 371 patients with either acute large-artery atherosclerosis or small-artery oc-clusion cerebral infarction were recruited to investigate the potential impact of elevated serum uric acid on cerebrovascular disorders. The results showed that patients who have suffered from large-artery atherosclerosis, relative to small-artery occlusion patients, were characterized by elevated serum uric acid but reduced high-density lipoprotein cholesterol and triglyceride levels. Logistic regression showed that elevated uric acid and lower triglyceride levels were the main risk factors for patients with large-artery atherosclerosis. The findings of this study suggest that hyperuricemia may be a risk factor for stroke.

Association of G-protein coupled purinergic receptor P2Y2 with ischemic stroke in a Han Chinese population of North China

The G-protein-coupled purinergic receptor P2Y2(P2RY2) plays an important role in the mechanism of atherosclerosis, which is relevant to ischemic stroke. This retrospective case-control study aimed to assess the relationship between P2RY2 gene polymorphisms and ischemic stroke risk in the northern Han Chinese population. In this study, clinical data and peripheral blood specimens were collected from 378 ischemic stroke patients and 344 controls. The ischemic stroke participants were recruited from the First Affiliated Hospital of China Medical University and the First Affiliated Hospital of Liaoning Medical University. The controls were recruited from the Health Check Center at the First Affiliated Hospital of China Medical University. Ischemic stroke patients were divided into two subgroups according to the Trial of ORG 10172 in Acute Stroke Treatment(TOAST) classification: large-artery atherosclerosis(n = 178) and small-artery occlusion(n = 200) strokes. All subjects were genotyped for three single nucleotide polymorphisms(rs4944831, rs1783596, and rs4944832) in the P2RY2 gene using peripheral venous blood samples. The distribution of the dominant rs4944832 phenotype(GG vs. GA+AA) differed significantly between small-artery occlusion patients and control subjects(odds ratio(OR) = 1.720, 95% confidence interval(CI): 1.203–2.458, P < 0.01). Multivariable logistic regression analysis revealed that the GG genotype of rs4944832 was significantly more prevalent in small-artery occlusion patients than in control subjects(OR = 1.807, 95% CI: 1.215–2.687, P < 0.01). The overall distribution of the haplotype established by rs4944831-rs1783596-rs4944832 was significantly different between ischemic stroke patients and controls(P < 0.01). In ischemic stroke patients, the frequency of the G-C-G haplotype was significantly higher than in control subjects(P = 0.028), whereas the frequency of the T-C-A haplotype was lower than in control subjects(P = 0.047). These results indicate that the G-C-G haplotype of P2RY2 is a susceptibility haplotype for ischemic stroke. In addition, the GG genotype of rs4944832 may be associated with the development of small-artery occlusion in the northern Han Chinese population. The study protocol was approved by the Ethics Committee of the First Affiliated Hospital of China Medical University on February 20, 2012(No. 2012-38-1) and the First Affiliated Hospital of Liaoning Medical University, China, on March 1, 2013(No. 2013-03-1). All participants gave their informed consent. This trial was registered with the ISRCTN Registry(ISRCTN11439124) on October 24, 2018. Protocol version(1.0).