Association Study Of PON1 Genetic Polymorphisms And Ischemic Stroke

Ischemic stroke is an acute neurological event resulting from vascular occlusion, which leads to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Based on the epidemiological surveys, ischemic stroke accounts for approximately 60%~80% of all strokes. It threatens lives and healthy of people severely for its high morbidity, high rate of mutilation, especially high mortality. And it gives heavy burden on the society, familial finance and human resources. Ischemic stroke is a kind of complicated syndrome caused by many diseases, under the influences of multiple environmental and genetic factors. Recently genetic researchs on ischemic stroke work deeper and deeper, and a plenty of stroke correlated candidate genes have been reported in different pathways, including lipid metabolism, inflammation, renin angiotensin system, apposition, homocysteic acid metabolism, coagulation/fibrinolysis system, and so on. In these years especially stroke genetic researches are focused on various correlative candidate genes in lipid metabolism pathway at home and abroad. Association analysis of candidate genes is the major approach in the genetic researches. The association analysis is the method that through comparisoning the single nucleotide polymorphisms (SNP) near the candidate genes between patients and health ones, we can obtain the ratios of geneotype and allele frequencies to find the pathogenic candidate gene. The association analysis based on haplotype map and haplotype tag SNPs has stronger statistic efficiency than the traditional single SNP, which can reduce large gene detection work.Artherosclerosis is the main pathophysiological foundation of ischemic stroke. In recent years, it has been known that lipid metabolism plays a key role in atherosclerosis. Through the study of associated candidate genes, we can research the ischemic stroke pathogenesis and provide theory proofs for screening the genes of susceptible population and personal therapy. As an important constituent of high density lipoprotein (HDL), paraoxonase1 (PON1) can protect HDL against oxidation, hydrolyze lipid peroxides, reduce peroxide modification of LDL, restrain the biosynthesis of cholesterin, depress the accumulation of cholesterin in macrophage. So it can check foam cells formation and forbid the happening of atherosclerosis. This research investigates the association between PON1 rs2299262 htSNP polymorphism and ischemic stroke, through genetic research in ischemic stroke patients and normal subjects of Chinese northern Han population.We recruited 529 ischemic stroke patients of department of neurology in the first clinical hospital of Jilin University from October 2005 to June 2006. All patients were fulfilled the diagnosis standards of ischemic stroke according to The 4th Cerebrovascular Diseases Academic Meeting of Chinese Medical Association in 1995, confirmed by CT or MRI investigations. In addition, ischemic stroke patients were sub-grouped into 304 large artery atherosclerotic infarction patients and 225 lacunar infarction patients based on TOAST standard. Control group was composed of 305 age-match and gender-match normal healthy subjects. We recorded all subjects'relative clinical documents in details. After abstraction genome DNA from blood, we detected all subjects PON1 rs2299262 htSNP polymorphism with PCR-RFLP. The Hardy-Weinberg (H-W) equilibrium was tested for genotype frequency distributions of htSNP using the goodness of fit test. To analysize and compare the genotype and allele frequencies distribution between case and control groups. Data were dealt with SPSS and UNPHASED statistics softwares to study the association between PON1 rs2299262 htSNP polymorphism and ischemic stroke, after t test, X2test and risk estimated test. We also investigate the association of PON1 rs2299262 htSNP polymorphisms with the level of plasma total cholesterol, plasma total triglyceride, HDL, LDL, fasting blood glucose and body mass index by quantitative trait analysis. Measurement data were presented with mean±standard deviation, and P<0.05 is the significance standard.The results of this research are as follows:①The H-W equilibrium: The goodness of fit test showed that genotype frequency distributions of all subjects were not deviated from the H-W equilibrium, hence these samples were suitable for the genetic analysis.②The results of clinical documents and laboratory examinations in control and case group prove the effect of risk factors in ischemic stroke as revealed previously. Patients with hypertension history, Diabetes Mellitus history, cigarette onsumption were obviously more than those in control group. And blood level, fasting blood glucose and blood lipid level were significant factors of ischemic stroke.③Association analysis of PON1 rs2299262 htSNP polymorphism and ischemic stroke: No significant difference was found in the genotype of PON1 rs2299262 htSNP polymorphism between the case and the control group (P>0.05).When subjects were divided into two subgroups, including large artery atherosclerotic infarction and lacunar infarction, rs2299262 htSNP T allele distribution differed significantly between large artery atherosclerotic infarction group and the control group. When divided them by gender, there was no association between the subgroups and control group. In conclusion, we study PON1 rs2299262 htSNP polymorphism in Chinese northern Han population. And we find that patients with PON1 rs2299262 htSNP T allele have a higher risk of large artery atherosclerotic infarction than without it. PON1 rs2299262 htSNP is probably a genetic determinant of large artery atherosclerotic infarction with high risk.