| Part ⅠRelationship between polymorphisms of C893T gene of platelet membrane receptor P2Y1 and cerebral infarctionObjectiveAdenosine diphosphate (ADP) is an important medium for platelet aggregation, and stimulates platelet activation and aggregation through the P2Y receptor.Mutations in the P2Y receptor gene can alter the activity of these receptors, thus affecting the aggregation function of platelets.At present, there are few studies about the P2Y1 gene polymorphism and cerebral infarction, and more focused on the study of aspirin and clopidogrel resistance, and the results of the study are still in dispute.This study aimed to determine the relationship between polymorphisms of C893T gene of platelet membrane receptor P2Y1 and cerebral infarction (CI) in Han population of North Shandong Province of China. At the same time, the general clinical data and some risk factors were collected, and the interaction between genetic and environmental factors in patients with cerebral infarction was studied。MethodsA case-control study of 162 healthy people (the normal contrast group) and 185 CI patients confrmed by computed tomography or magnetic resonance imaging (CI group) was conducted, the clinical data were recorded in two groups (including age, gender, smoking, drinking, shrinkage pressure, diastolic blood pressure, blood glucose, cholesterol, triglyceride, low density lipoprotein, high density lipoprotein, serum uric acid, fibrinogen, homocysteine).The polymorphisms were tested by polymerase chain reaction and restriction fragment length polymorphism analysis (PCR-RFLP). The distribution characteristics in normal people and CI patients, as well as the relationship between the polymorphisms of C893T gene of platelet membrane receptor P2Y1 and ischemic stroke, were analyzed.ResultsNo signifcant differences in age, gender composition, alcohol consumption, blood glucose, cholesterol, triglyceride, low density protein, high density lipoprotein cholesterol, uric acid,and homocysteine were found between the contrast group and CI group (P>0.05). By contrast, signifcant differences were found in smoking, systolic pressure, diastolic blood pressure, and plasma fbrinogen level between contrast and CI groups (P<0.05 or P<0.01). Genotyping revealed 149 carriers of the wild-type CC genotype and 36 carriers of the mutational T allele of P2Y1 C893T in the CI group, and 148 carriers of the wild-type CC genotype and 14 carriers of the mutational T allele of P2Y1 C893T in contrast group. The TC/TT gene frequencies (19.46%) in the CI group was much higher (X2=8.195, P<0.01) than that of contrast group (8.64%). The frequencies of T allele in the CI and contrast groups were 10.81% and 4.63%, respectively, showing signifcant difference (X2=9.045, P<0.01). Multiple logistic regression analysis showed that factors associated with CI include systolic blood pressure, plasma fbrinogen level, and carrying-893T gene. After controlling for potential confounding factors,-893T allele carriers had a 2.065-fold increased risk for CI (OR=2.065,95% confdence interval:1.011-4.218, P=0.046) compared with non-carriers.Conclusion and significanceThis study found that smoking, hypertension and elevated plasma fibrinogen level is an important risk factor for ischemic stroke, also confirmed that platelet membrane glycoprotein receptor P2Y1 C893T gene TC/TT is likely a risk factor of ischemic stroke. This study further defined the single nucleotide polymorphism plays a certain role in the pathogenesis of cerebral infarction and confirmed that the C893T polymorphism of P2Y1 gene is one of the genetic susceptibility genes of cerebral infarction,to provide a theoretical basis for the prevention and treatment of ischemic stroke.Part ⅡRelationship between polymorphisms of H1/H2 gene of platelet membrane receptor P2Y12 and cerebral infarctionObjectivePlatelets play a key role in the pathophysiology of thrombosis after plaque rupture, and P2Y genotype in different aspects of the formation there may be differences in platelet aggregation and arterial thrombosis, the latter two is the pathological basis of ischemic stroke.This study aimed to determine the relationship between polymorphisms of H1/H2 gene of platelet membrane receptor P2Y12 and cerebral infarction (CI) in Han population of North Shandong Province of China. At the same time, the general clinical data and some risk factors were collected, and the interaction between genetic and environmental factors in patients with cerebral infarction was studied。MethodsA case-control study of 168 healthy people (the normal contrast group) and 152 CI patients confrmed by computed tomography or magnetic resonance imaging (CI group) was conducted, the clinical data were recorded in two groups (including age, gender, smoking, drinking, shrinkage pressure, diastolic blood pressure, blood glucose, cholesterol, triglyceride, low density lipoprotein, high density lipoprotein, serum uric acid, fibrinogen, homocysteine).The polymorphisms were tested by polymerase chain reaction and restriction fragment length polymorphism analysis (PCR-RFLP). The distribution characteristics in normal people and CI patients, as well as the relationship between the polymorphisms of H1/H2 gene of platelet membrane receptor P2Y12 and ischemic stroke, were analyzed.ResultsNo signifcant differences in age, gender composition, smoking, alcohol consumption, blood glucose, cholesterol, triglyceride, low density protein, high density lipoprotein cholesterol, uric acid,and homocysteine were found between the contrast group and CI group (.P>0.05). By contrast, signifcant differences were found in systolic pressure, diastolic blood pressure, and plasma fbrinogen level between contrast and CI groups (P<0.01). 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 Hl/Hl genotype and 28 carriers of the mutational H2 allele of P2Y12 H1/H2 in contrast group. The H1/H2 and H2/H2 gene frequencies (26.3%) in the CI group was much higher (X2=4.440, P<0.05) than that of contrast group (16.7%). The frequencies of H2 allele in the CI and contrast groups were 14.5% and 8.6%, respectively, showing signifcant difference (X2=5.392, P<0.05). Multiple logistic regression analysis showed that factors associated with CI include systolic blood pressure, plasma fbrinogen level, and carrying-893T gene. After controlling for potential confounding factors, H2 allele carriers had a 1.928-fold increased risk for CI (OR=1.928,95% confdence interval:1.137-3.188, P=0.038) compared with non-carriers.Conclusion and significanceThis study found that hypertension and elevated plasma fibrinogen level is an important risk factor for ischemic stroke, also confirmed that platelet membrane glycoprotein receptor P2Y12 gene H1/H2 and H2/H2 is likely a risk factor of ischemic stroke,and provide a theoretical basis for the prevention and treatment of ischemic stroke. |
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