The Association Of PON2 C311S And Fibrinogen β-455G/A Genetic Polymorphism With Cerebral Infarction In Chinese

Background:Cerebrovascular disease is the leading cause of death and disability. Both treatment and nursing of these patients are very expensive. Atherosclerosis(AS) is a leading cause of cerebral infarction, especially the arterothrombtic cerebral infarction(ACI). Abnormal metabolism of lipid, particularly the oxidation of low density lipoprotein and content of plasma fibrinogen(Fg), are two important factors for the development of AS. Oxidized low density lipoprotein(ox-LDL) plays an important role in the process of AS, which involves early activation, malfunction and late functional disorders of endothelium. Study and reseach show that there is a close correlation between the formation of ox-LDL and activity of paraoxonase families(PONs). There are lot of reports about the correlation between paraoxonase1(PON1) and cerebral infarction, but few reports about the correlation between paraoxonase2(PON2) and cerebral infarction. High expression of plasma Fg is, on the one hand, easy to form thrombus and on the other hand, it promotes AS. Both function and expression of PON2 and plasma Fg are affected by genetic polymorphism. The frequency of both PON2 and Fg gene distribution is different from race to race and from region to region, and the association of frequency of their gene distribution with cerebral infarction is also different too. Objective: ①To investigate whether there is gene polymorphism of PON2 C311S and Fgβ-455G/A in Nanning, and compare with other areas.②To investigate the relationship between gene polymorphism of PON2 C311S and plasma lipid level and whether the mutation at this point is associated with ACI.③To investigate the relationship between gene polymorphism Fgβ-455G/A and plasma Fg level and whether A allele is associated with ACI. Methods: A case-control study was used. Gene polymorphism of PON2 C311S and Fgβ-455G/A were analyzed by PCR, PCR-RFLP with restrictive enzyme DdeⅠand HaeⅢrespectively in 108 cases of ACI and 75 cases of the control group of nonthrombosis and 123 cases of health adults. Results: ①There is gene polymorphism of PON2 C311S and Fgβ-455G/A in Nanning, SS and GG are common genetypes, freqency of C/S allele 0.203/0.797, and there is some differences in comparation with other races of people or people in other regions; G/A allele 0.789/0.211, and there is a difference in domestic areas. ②Freqency of 311C allele of PON2 is significant high in those patients of ACI than in the control group(ACI vs health adult P=0.0007), for it may affect the function of the apoenzyme, but its polymorphism does not lead to the change of plasma lipid and plasma viscosity. ③Freqency of -455A allele of Fgβis higher in those patients of ACI than in the control group(ACI vs health adult P=0.0464), because it may affect fibrin polymeric function. But its polymorphism does not lead to the change of level of plasma Fg either. ④The metabolic disorder of plasma lipid,higher level of plasma Fg and plasma viscosity in ACI group are notable (P<0.05). Conclusion: ①There is gene polymorphism in code 311 of PON2 No.9 exon and -455 of Fgβin Nanning, SS and GG are common genetypes, freqency of C/S allele 0.203/0.797, G/A allele 0.789/0.211. There is a difference in comparation with other races of people or people in other regions. ②Levels of plasma lipid and plasma viscosity are not affected by the polymorphism of PON2 C311S, and level of plasma Fg not affected by the polymorphism of Fgβ-455G/A too. But the metabolic disorders of plasma lipid, higher level of plasma Fg and plasma viscosity in ACI group are remarkable. ③There is association of 311C allele of PON2 and -455A allele of Fgβwith ACI in Chinese.