Association Of Lipoprotein-associated Phospholipase A2 Gene R92H And V279F Polymorphisms With Susceptibility And Recurrence Of Ischemic Stroke

Background The pathogeny of ischemic stroke is complex. Traditional vascular danger factor,such as hypertension, hiperlipemia, diabetes mellitus,smoking,drinking,obesity has been known for long time.But in recent years,hereditary factors, role in vascular atherosclerotic has been recognized by searcher.It has important meaning to take early prevention and guide the treatment to ischemic stroke by analysising the role of hereditary factors in stroke.Inflammation and oxcidative stress have immportant role in the progress of atherosclerosis deseases.Vascular endothelial cells can have essential changes after receiving damaging stimulation such as smoking,hypertention,hyperglycemia,hyperlipidemia.It was called”endothelial activation”.This is the earliest event of atherosclerosis.Activated endothelium cells secrete adhsion molecule and chemotaxis factor.The permeability of endothelium is enhanced.At the bottom of endothelium,the structure of stroma outside of endothelium cells take changes.So low density lipoprotein,especialy those smaller and denser one have stronger proatherosclerosis. Deep vascular endothelial, gathered in the intima, and oxidized in there. Oxidized LDL can make the aggregation of monocytes and promote the conversion into macrophage.The latter can devour Oxidized LDL and convert into foam cells.This is the most essencial part of fatty streak.Clinical symptom appear when atherosclerosis attach some consent,such as arterial lumen stenosis can cause the Insufficiency of blood supply and oxygen supply of organ, manifestation of angina pectoris, transient ischemic attack, Intermittent Po line, unstable plaque rupture, local thrombus formation, acute myocardial infarction,stroke et al.Many studies have found atherosclerotic thrombosis closely related to ischemic cerebrovascular disease is not consistent with the degree of vascular stenosis caused by atherosclerotic plaque and it is mainly related to the nature of the patch. More specifically speaking, is correlated with the degree of local inflammation, take fibrous plaque thickness, plaque degradation related inflammatory cytokines, metalloproteinase. This may explain why many patients with mild plaque have severe arterial ischemic events.One of the hot spots in the study of cerebrovascular diseases was found to predict the value of circulating markers of ischemic cerebrovascular disease. C reactive protein, cholesterol levels and other previous studies of marker of ischemic cerebrovascular disease forecast value smaller, looking for carotid artery plaque stability in value prediction model circulating markers in clinical research is necessary. Lipoprotein associated phospholipase A2(Lp-PLA2), is a member of the phospholipase A2 protein amily, in the oxidized LDL proinflammatory phospholipase and atherogenic metabolic products such as oxidation and lysophosphatidylcholine(lysophosphatidylcholine) fat acid(oxidized free fatty acids produced in play an important role.Study on Lp-PLA2 gene polymorphism. It is found that in 9 exons are involved in pathogenesis of sub v279 f sites with the Japanese coronary heart disease and stroke, located in 11 exons are involved in pathogenesis of sub A379 V polymorphisms and coronary heart disease in Korea and ischemic stroke in China, but there is no about in the fourth exon on the R92 H sites and v279 f sites and Chinese ischemic cerebral stroke risk of research. Therefore, this study mainly related to the R92 H and V279 F loci and the risk of ischemic stroke and different subtypes of ischemic stroke in mainland China.Objective 1.To explore the distribution difference of the distribution characteristics of two polymorphisms in ischemic stroke patients and normal control population lipid protein associated phospholipase A2(Lp-PLA2) gene R92 H and v279 f study and comparison of ischemic stroke patients and normal controls, two locus genotype and gene frequency; 2.The TOAST of Lp-PLA2 gene polymorphism R92 H and although v279 f two sites and Chinese Han population of ischemic cerebral stroke patients with vascular risk factors and stroke type, blood lipid analysis and prognosis between relationship analysis, and to evaluate the role of Lp-PLA2 in the onset and development of ischemic stroke.Method 1.Collected by brain MRI or CT confirmed ischemic stroke patients and normal controls, collect ischemic stroke of traditional vascular risk factors, such as age, gender, family history, hypertension, diabetes, hyperlipidemia, smoking, drinking history. 2.Fasting venous blood was taken from the forearm and the blood genomic DNA extraction kit was used to extract the white blood cell DNA. 3.Polymorphism of Lp-PLA2 gene was determined by R92 H and V279 F two loci by PCR and gene sequencing, and two loci genotype and allele frequency in the ischemic stroke group and control the distribution of coarse comparison. 4.Analysis of the relationship between the polymorphism of two genetic loci and the incidence and prognosis of ischemic stroke.Result 1.A total of 386 ischemic stroke patients included in this study, after toast subtypes classified LAA group of 254 cases with Sao group(132 cases), LAA group, with an average age of 62.1 ±9.89 years old, 68.9% of the male, Sao group, with an average age of 24.8 2.64 + year old male 69.7%. The control group of 386 cases, the average age of 61.9 ± 9.84 years old, IS traditional risk factors such as hypertension, diabetes, hyperlipidemia, smoking, drinking, TIA history of the previous IS group was significantly higher than the control group. 2. The level of serum Lp-PLA2 in ischemic stroke(IS) group was significantly higher than that in the control group, there was significant difference(P<0.01). Compared with the control group, the serum Lp-PLA2 levels in LAA group and SAO group were higher than those in the control group, and there was significant difference.3. Ischemic cerebral stroke group Apo A1, mean HDL-C levels were significantly lower than those in the control group, and fasting blood glucose(FBG) average was significantly higher than that of control group, triglyceride(TG), low density lipoprotein cholesterol(LDL-C) average in the stroke group was significantly lower than that of the normal control group. 4. The frequency of AA+GA genotype of R92 H locus in the IS group was significantly higher than that in the control group, the difference was significant(30.8%, P=0.009). The frequency of A allele of R92 H in IS group was significantly higher than that in control group, the difference was significant(16.5%, P=0.001). The expression frequency of VF+FF genotype in IS group was significantly higher than that in control group, and the difference was significant(30%, p=0.007). The expression rate of VF gene in V279 F was higher in group IS(28%, P=0.004). The frequency of F allele in the V279 F group was significantly higher than that in the control group(15.8%, P=0.002) in the IS group. 5. R92 H sites of GA,GA+AA genotype is significantly related to LAA, and Sao type of stroke and each genotype association is not obvious. VF+FF genotype and gene type of VF and LAA stroke was significantly related to(2=10.837, P = 0.003; 2=9.366, P = 0.006), and Sao stroke and the base for the allele frequencies of type and no significant correlation(P > 0.05). 6. Logistic regression analysis showed that, R92 H sites GA, AA+GA genotype and A allele is associated with IS(respectively group, OR=1.43,95%CI=1.03-1.98,p=0.032;OR=1.47,95%CI=1.07-2.02,p=0.027;OR=1.42,95%CI=1.07-1.89,p=0.024), V279 V VF+FF genotype and F, the gene and is significantly correlated(both of which were OR=1.42,95%CI=1.03-2.04, P = 0.028; OR = 1.42, 95%CI=1.07-2.24, P = 0.031). 7. Cox regression analysis showed that the R92 H genotype was associated with recurrence in patients with IS. Among them, the GA+AA genotype was associated with the recurrence of IS(OR=1.75,95%CI=1.03-2.29, P=0.041), and the V279 F genotype was associated with recurrence in patients with IS. Among them, the VF+FF genotype was associated with the recurrence of IS(OR=1.72,95%CI=1.01-2.35, P=0.039).Conclusion 1.The level of serum Lp-PLA2 was closely related to the incidence of ischemic stroke, and the level of Lp-PLA2 in the ischemic stroke group was significantly higher than that in the control group. 2.Polymorphisms of Lp-PLA2 gene R92 H and Chinese Han ischemic stroke onset is closely related, genotype GG + GA, GA genotype and A allele frequencies are significantly increased in the ischemic stroke group; R92 H gene polymorphism and LAA stroke has obvious relationship, and with the SVO type no significant. 3.The allele frequencies of Lp-PLA2 gene v279 f sites FF+VF genotype, VF gene type and F were correlated with the onset of ischemic stroke in Chinese Han population, although v279 f gene polymorphism and LAA stroke has obvious relationship, and with the SVO type had no significant relationship. 4.R92 H and V279 F loci were associated with ischemic stroke recurrence, and the relationship between and LAA was more closely related to stroke.