Platelet membrane receptor P2Y12 H1/H2 polymorphism is highly associated with cerebral infarction: a case-control study

Abstract

Objectives: This study aimed to determine the relationship between the polymorphisms of the H1/H2 gene of platelet membrane receptor P2Y12 and cerebral infarction (CI) in a Han population in North Shandong Province, People's Republic of China.

Patients and methods: A case-control study, which involved 168 nonstoke subjects (contrast group) and 152 CI patients (CI group), was conducted. The state of subjects in the CI group was validated by computed tomography or MRI. The clinical data were categorized into two groups. The data included age, gender, smoking, drinking, shrinkage pressure, diastolic blood pressure, blood glucose, cholesterol, triglyceride, low-density lipoprotein, high-density lipoprotein, serum uric acid, fibrinogen and homocysteine. The polymorphisms were genotyped with PCR and restriction fragment length polymorphism analysis. The distribution characteristics of nonstoke subjects and CI patients and the relationship between the polymorphisms of the H1/H2 gene of platelet membrane receptor P2Y12 and ischemic stroke were analyzed.

Results: No significant difference was found between the contrast group and CI group (P>0.05) in terms of age, gender composition, smoking, alcohol consumption, blood glucose, cholesterol, triglyceride, low-density protein, high-density lipoprotein cholesterol, uric acid and homocysteine. In contrast, significant differences were found between these two groups (P<0.01) in terms of SBP, DBP and plasma fibrinogen level. The genotyping revealed 112 carriers of the wild-type H1/H1 genotype and 40 carriers of the mutational H2 allele of P2Y12 H1/H2 in the CI group and 140 carriers of the wild-type H1/H1 genotype and 28 carriers of the mutational H2 allele of P2Y12 H1/H2 in the contrast group. Furthermore, the H1/H2 and H2/H2 gene frequencies (26.3%) were significantly higher in the CI group (χ²=4.440, P<0.05) than those in the contrast group (16.7%). Moreover, the frequencies of the H2 allele in the CI and contrast groups were 14.5% and 8.6%, respectively, and the difference was statistically significant (χ²=5.392, P<0.05). Multiple logistic regression analysis results revealed that factors associated with CI include systolic blood pressure and plasma fibrinogen level, which carry the -893T gene. After adjusting for potential confounding factors, the H2 allele carriers had a 1.928-fold increased risk for CI (OR=1.928, 95% confidence interval: 1.137-3.188; P=0.038) when compared with noncarriers.

Conclusion: The present study found that hypertension and elevated plasma fibrinogen levels are significant risk factors for ischemic stroke and confirmed that the H1/H2 and H2/H2 genes of platelet membrane glycoprotein receptor P2Y12 are risk factors of ischemic stroke.

Keywords: P2Y12 gene; adenosine diphosphate; clopidogrel resistance; ischemic stroke; single-nucleotide polymorphism.

Figure 1

P2Y12 gene electrophoretogram. Notes: M denotes the indicator “Mark”: the index strip from top to bottom is 250 bp, 220 bp, 200 bp, 170 bp and 150 bp. (1 and 6) The PCR product: 230 bp. (2) H1/H1: 197 bp; (3 and 5) H1/H2: 197 bp and 157 bp. (4) H2/H2: 157 bp. Magnification 1:1.