Plain English Summary
Background and study aims
People in northern China are at an increased risk of ischemic stroke (damage to the brain caused by narrowing of blood vessels in the brain). This study aimed to investigate if gene forms linked to increased risk of stroke are more common in Han Chinese people in this region.
Who can participate?
People aged 45-80 years who had had an ischemic stroke and healthy volunteers matched in terms of age, gender, ethnic group and area of residence with the stroke group.
What does the study involve?
One sample of blood was taken from a vein (usually in the arm).
What are the possible benefits and risks of participating?
There was the potential for discomfort when the blood was taken. There are no potential benefits of taking part.
Where is the study run from?
The First Affiliated Hospital of China Medical University.
When is the study starting and how long is it expected to run for?
The samples were collected from September 2010 to May 2011 and the data analysed from March 2012 to April 2012.
Who is funding the study?
This study was supported by a grant from the National Natural Science Foundation of China, No. 81070913.
Who is the main contact?
Dr Li-Ying Yuan
Nanjing North Street
G-Protein Coupled Purinergic Receptor P2Y2 (P2RY2) gene rs4944832 polymorphism increases the risk of ischemic stroke in the northern Han Chinese population
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.
1. Ethics Committee of the First Affiliated Hospital of China Medical University, 20/02/2012, 2012-38-1
2. Ethics Committee of the First Affiliated Hospital of Liaoning Medical University, 01/03/2013, 2013-03-1
Observational case-control study
Primary study design
Secondary study design
Patient information sheet
No participant information sheet available
In this study, clinical data and peripheral blood specimens were collected from ischemic stroke patients and 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 using SNaPshot® Multiplex (Thermo Fisher Scientific) for three single-nucleotide polymorphisms in the P2RY2 gene (rs4944831, rs1783596 and rs4944832) in peripheral venous blood.
Primary outcome measure
The genotype frequencies of the three P2RY2 SNPs (rs4944831, rs1783596, and rs4944832) in ischemic stroke patients and controls.
Secondary outcome measures
1. Allele frequencies of the three P2RY2 SNPs (rs4944831, rs1783596, and rs4944832) in ischemic stroke patients and controls.
2. Inferred haplotypes of these three P2RY2 SNPs (rs4944831, rs1783596, and rs4944832).
Overall trial start date
Overall trial end date
Reason abandoned (if study stopped)
Participant inclusion criteria
Inclusion criteria for the ischemic stroke group:
1. According to the TOAST classification, patients in the ischemic stroke group were diagnosed depending on clinical features and neuroimaging criteria that included the sudden onset of a global or focal neurological deficit, with corresponding brain infarction as seen on computed tomography (CT) imaging or magnetic resonance imaging (MRI) (Adams et al., 1993). Examinations of cerebral blood vessels, such as computed tomography angiography and magnetic resonance angiography, were performed when necessary.
Inclusion criteria for the control group:
1. Unrelated healthy controls with no clinical or radiological evidence of stroke or cerebrovascular diseases.
2. Some healthy controls had vascular risk factors such as hypertension, diabetes, smoking, drinking, and hypercholesterolemia.
Target number of participants
Participant exclusion criteria
Exclusion criteria for the ischemic stroke group:
2. Hemorrhagic stroke
3. Transient ischemic attack
4. Severe cardiac, hepatic, or renal diseases
Exclusion criteria for control subjects:
2. Autoimmune disease
3. Chronic inflammation
4. Renal insufficiency
5. Liver insufficiency
Recruitment start date
Recruitment end date
Countries of recruitment
Trial participating centre
The First Hospital of China Medical University
No.155, Nanjing North Street, Heping District
Trial participating centre
The First Affiliated Hospital of Liaoning Medical University
No.2, Section 5, Renmin Street, Guta District
the First Hospital of China Medical University
Nanjing North Street
National Natural Science Foundation of China
National Science Foundation of China, Natural Science Foundation of China, Chinese National Science Foundation, NSFC
Funding Body Type
Funding Body Subtype
Results and Publications
Publication and dissemination plan
IPD sharing statement:
The data sharing plans for the current study are unknown and will be made available at a later date.
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
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). Multivariate 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).
The percentages of individuals with hypertension, diabetes, current smoking status, or current alcohol consumption were higher in ischemic stroke patients (LAA: 178, SAO: 200) than in controls (Table 2). Levels of serum fasting plasma glucose, total cholesterol, and LDL-C were also higher in ischemic stroke patients than in controls.
The genotype distributions of the three SNPs (rs4944831, rs1783596, and rs4944832) were in Hardy–Weinberg equilibrium in both patients and controls (P > 0.05). There was no significant difference in the distributions of each SNP between ischemic stroke patients and controls (P > 0.05).
There were no significant differences in the rs4944831 and rs1783596 genotypes or allele distributions between ischemic stroke patients and controls. In contrast, there were significant differences in the distributions of the GG genotype and of the G allele of rs4944832 between SAO patients and control subjects (P < 0.01). However, this difference was not observed in patients with LAA. Multivariate logistic regression analysis was used to assess the relationship between the rs4944832 polymorphism and SAO by adjusting for confounding variables.
Using the SHEsis program platform, these P2RY2 SNPs (rs4944831, rs1783596, and rs4944832) were found to be in linkage disequilibrium in the Chinese population. Six haplotypes with frequencies greater than 3% among both ischemic stroke patients and control subjects were selected in the haplotype analysis.
2018 results in: https://www.ncbi.nlm.nih.gov/pubmed/30539820